Microbiome analysis of adenolymphangitis-causing bacteria in filarial lymphedema patients
| ISRCTN | ISRCTN48705786 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN48705786 |
- Submission date
- 29/12/2024
- Registration date
- 15/01/2025
- Last edited
- 14/03/2025
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Infections and Infestations
Plain English summary of protocol
Background and study aims
Filarial lymphedema is a symptom of lymphatic filariasis, a disease caused by microscopic parasitic worms that are transmitted to humans by mosquitoes. Patients with filarial lymphedema suffer from episodes of adenolymphangitis (ADL) attacks. ADL attacks are painful inflammatory episodes, presenting with fever, inflammation of the affected limbs, malaise and other symptoms that result in the patients being unable to perform normal duties for days. Basic hygiene interventions have been shown to reduce episodes of ADL attacks. In addition to ADL contributing to loss of income due to the patients being unable to perform normal duties, it has also been shown to lead to lymphedema progression.
The exact cause of ADL attacks still remains unknown, although secondary bacterial infections that get access through cracks in the skin have been thought to trigger the attacks.
Using next-generation sequencing (NGS) to analyze pathogens (bacteria) in blood samples collected from lymphedema patients, this study aims to identify organisms associated with the inflammatory episode. In addition to the assessment of blood, NGS will be performed on swabs collected from the affected and unaffected limbs as well as sentinel sites (belly bottom and groin) and wounds to identify differences in pathogen composition before and during an acute attack. Additionally, follow-up samples will be collected after the identification of medically interesting pathogens, to test for antimicrobial sensitivity.
Who can participate?
Lymphedema participants aged 18 years or older willing to join the study in the study region and non-lymphedema patients as controls
What does the study involve?
Blood samples and swab sets (always three pairs of swabs: two from each leg, two pooled from the belly button and from the groin crease) will be collected at the study start (baseline) and during an ADL attack. In addition, swabs might also be taken from wounds (e.g., parts of the legs where there are skin cracks, secretion of tissue fluid and skin lesions).
Blood and swabs will be collected for performing NGS, culture and antimicrobial sensitivity (AST), and immunology. If pathogens of medical importance are found in the blood through either blood cultures or NGS during ADL attacks, NGS will be performed on the set of swabs. For controls (without LE), only baseline sampling involving the collection of skin swabs and blood will be done.
What are the possible benefits and risks of participating?
The benefits for participants are training and supplies for local care of lymphedema. In addition, medication needed to alleviate an ADL attack will be provided. Medically relevant findings (including incidental findings) from the examinations and sample analysis can be obtained if desired.
There is no risk for the participant from swab sampling of the healthy skin. The equipment for taking skin swabs will be sterile and only handled by trained staff. Swabbing the wounds may cause local pain and irritations. In some cases, there might be an increased risk of infection. If this occurs, appropriate treatment will be provided.
The potential risks of the needle stick for blood drawing include pain, fainting, infection and bruising, or a small hematoma. The bruising may last up to 72 hours. Rarely, a swelling (hematoma) may appear which is easily treated with local pressure. Infections from the needle puncture are rare, but if this does occur, appropriate treatment will be given. In very rare cases, blood sampling can lead to nerve lesions, which could be permanent.
Where is the study run from?
National Institute for Medical Research (NIMR) and Sokoinne Referral Hospital, Lindi, Tanzania
When is the study starting and how long is it expected to run for?
December 2022 to March 2028
Who is funding the study?
German Federal Ministry of Education and Research (BMBF) Research Networks for Health Innovations in Sub-Saharan Africa
Who is the main contact?
Dr Abdallah Ngenya, abdallah.ngenya@nimr.or.tz
Contact information
Public, Scientific, Principal Investigator
3 Barack Obama Drive
Dar es Salaam
11101
Tanzania
| Phone | +255 (0)719223937 |
|---|---|
| abdallah.ngenya@nimr.or.tz |
Scientific
Venusberg-Campus 1
Bonn
53127
Germany
 ORCID ID |
0000-0002-8671-3831 |
|---|---|
| Phone | +49 (0)228 28715673 |
| achim.hoerauf@ukbonn.de |
Study information
| Study design | Prospective cohort study |
|---|---|
| Primary study design | Observational |
| Secondary study design | Cohort study |
| Study setting(s) | Home, Laboratory, Medical and other records |
| Study type | Diagnostic, Quality of life, Screening |
| Participant information sheet | Not available in web format, please use contact details to request a participant information sheet |
| Scientific title | TAKeOFF – microbiome analysis of adenolymphangitis-causing bacteria in filarial lymphedema patients: a study in the Lindi region |
| Study acronym | TAKeOFF-Microbiome-TZ |
| Study objectives | The aim of this study is to identify pathogens associated with adenolymphangitis (ADL) attacks using next-generation sequencing, and testing antimicrobial sensitivity, with the aim of providing better treatment options in morbidity management |
| Ethics approval(s) |
1. Approved 31/10/2024, Medical Research Coordination Committee (MRCC) (3 Barack Obama Drive, Dar es Salaam, 11101, Tanzania; +255 22 2121400; ethics@nimr.or.tz), ref: NIMR/HQ/R.8a/Vol.IX/4742 2. Approved 10/12/2024, Ethics Committee at the Medical Faculty of the University Bonn (Venusberg-Campus 1, Bonn, 53127, Germany; +49-228-287-51931; ethik@ukbonn.de), ref: 2024-34-BO |
| Health condition(s) or problem(s) studied | Filarial lymphedema |
| Intervention | Blood samples and skin swabs will be collected from LE patients during baseline and at the onset of an ADL attack, to identify organisms associated with episodes of adenolymphangitis (ADL) attacks in LE patients. Analysis will be done using next-generation sequencing (NGS) and culture methods. Follow-up samples will be collected after the identification of medically interesting pathogens, to test for antimicrobial sensitivity. |
| Intervention type | Other |
| Primary outcome measure | 1. Identification of bacteria and fungi in blood collected during ADL attacks (V2 or/and V3) up to species level with NGS (mainly 16/18s) and blood culture (identification with MALDI-TOF or Vitek 2 Compact System) before and during attacks 2. Identification of bacteria and fungi from skin swabs of the same participant taken at ADL and baseline (V1), using NGS and cultures from cryopreserved microbial isolates (for methods of identification see above), and NGS from blood samples taken at V1 3. Identification of changes or similarities in bacteria and fungi from blood and skin swabs in ADL and baseline samples (for identification methods see above) 4. Assessment of antimicrobial sensitivity of bacteria and/or fungi of medical interest, identified in outcomes 1-2, primarily using Vitek AST |
| Secondary outcome measures | 1. Similarities or changes in the microbiome of LE participants at baseline and during ADL, compared to that of participants in the control group at baseline, measured with NGS (mainly 16/18s) and blood culture (identification with MALDI-TOF or Vitek 2 Compact System) 2. Similarities or changes between the microbiome of participants grouped by lymphedema stage measured using collected study data at baseline and during ADL with NGS (mainly 16/18s) and blood culture (identification with MALDI-TOF or Vitek 2 Compact System) 3. Immune response during ADL attacks is analyzed from whole blood samples collected at baseline and ADL. Peripheral Blood Mononuclear Cells (PBMCs) and plasma are prepared. In PBMCs, the immune cell populations (e.g., T cells and granulocytes) are analyzed using flow cytometry. Plasma is used to analyze pro-inflammatory and Th1/Th2/Th17 immune responses and chemokines using Luminex and ELISA techniques. |
| Overall study start date | 01/12/2022 |
| Completion date | 31/03/2028 |
Eligibility
| Participant type(s) | Healthy volunteer, Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 200 |
| Key inclusion criteria | 1. Lymphedema of at least one leg (cases) 2. Participants without lymphedema (controls) 3. Aged 18 years and above 4. Able and willing to provide informed consent (or assent, where applicable) to participate in the study |
| Key exclusion criteria | 1. Any significant condition (including medical and psychological/psychiatric disorders) that, in the opinion of the study clinician, might interfere with the conduct of the study 2. Lymphedema of non-filarial origin |
| Date of first enrolment | 12/03/2025 |
| Date of final enrolment | 31/12/2025 |
Locations
Countries of recruitment
- Tanzania
Study participating centres
Dar es Salaam
11101
Tanzania
Lindi
0000
Tanzania
Sponsor information
Research organisation
3 Barack Obama Drive
Dar es Salaam
11101
Tanzania
| Phone | +255-22-2121400 |
|---|---|
| info@nimr.or.tz | |
| Website | http://www.nimr.or.tz/ |
"ROR" |
https://ror.org/05fjs7w98 |
Funders
Funder type
Government
No information available
Results and Publications
| Intention to publish date | 30/09/2028 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | The results of the study will be reported to the in-country NTD programme, presented at scientific and program-related meetings, and published in peer-reviewed scientific journals. |
| IPD sharing plan | The data-sharing plans for the current study are unknown and will be made available at a later date. |
Editorial Notes
14/03/2025: The recruitment start date was changed from 14/01/2025 to 12/03/2025.
30/12/2024: Study's existence confirmed by the Medical Research Coordination Committee (MRCC).
