Malaria, Malaria Vaccine, Insecticide-treated BednetsRTSS/PBONCT04327440
RTSS Vaccine and PBO Net Impact on Malaria Infection and Transmission in Malawi
An observational study of Malaria, Malaria Vaccine, Insecticide-treated Bednets, run by Michigan State University at 1 site in Malawi.
Trial summary
The overall goal of this study is to assess the impact of RTS,S (malaria) vaccination and PBO nets on malaria infection and transmission, independently and how they interact when they are introduced together. The specific objectives for the study are as follows: 1. Read more about this study
- Who is it for?
- Ages 7 months to 10 yearsHealthy volunteers can take part
- Conditions the study is for
- Malaria, Malaria Vaccine, Insecticide-treated Bednets
- What is being tested?
- RTS,S/AS01 malaria vaccine and PBO bed nets
- Type of treatment
- Vaccines
- How many people
- 1,691 participants
- Where
- 1 siteMalawi
- Study dates
- 4 Feb 2020to 30 Jun 2021
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 7 months to 10 years
- All sexes
- Healthy volunteers accepted
- Child
Study population: Children whose age is between 7 and 18 months, which indicates they could receive at least 3 RTS,S doses, will be eligible to participate. Following informed consent from parents/guardians, up to two children who are 18 months but ≤10 years of age, from the same household as the vaccine-eligible child, will also be enrolled. Only households whose families intend to stay in the area for at least six months and whose eligible children will also be expected to use an assigned health center for child vaccinations will be eligible to participate.
Who may be able to join
- Children aged 7 to 18 months of age (age-eligible for at least 3 doses of RTS,S doses) OR being one of not more than two children living in the household of an enrolled age-eligible child and being >18 mos and < 10 years of age.
- Not on cotrimoxazole prophylaxis for HIV infection
- Weight >5 kg
- Permanent residence of Health Centre (HC) catchment area
- Residence within 10 km from the HC
- Written informed consent from parent/guardian for the child to participate in the study
Who cannot join
- Non-residents of the catchment area and visitors to the study area will be excluded because the study requires follow-up for at least 6 months and access to interventions such as conventional, PBO nets and malaria vaccination.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Combined Effects of RTS,S Vaccination and PBO Nets on Malaria Infection and Transmission in Malawi
The overall goal of this study is to assess the impact of RTS,S (malaria) vaccination and PBO nets on malaria infection and transmission, independently and how they interact when they are introduced together.
The specific objectives for the study are as follows:
- To estimate the impact of PBO nets and RTS,S vaccine on Plasmodium infection prevalence and transmission, independently and how they interact when they are introduced together in Malawi (Phase 1).
- To assess the feasibility of evaluating the impact of RTS,S vaccine and PBO nets independently in a larger scale future study.
Read the detailed description
Introduction: The decline in malaria incidence has stalled globally and incidence is increasing in some high transmission settings of sub-Saharan Africa, including Malawi. The situation is worsening despite the scale-up of previously effective interventions, raising concerns that the impact of current malaria control and prevention strategies maybe compromised.
Problem: There is an urgent need for innovative approaches to malaria control and Malawi is currently positioned to assess two of the most promising new interventions. The Malawi Ministry of Health (MOH) is launching large scale projects to evaluate a new formulation of insecticide-treated bed nets with a chemical synergist, piperonyl butoxide (PBO), designed to enhance the insecticidal effect of pyrethroids and the new malaria vaccine RTS,S (RTS,S). In an effort to gain the most information from these, interventions Malawi's National Malaria Control Programme (NMCP) have invited the Malawi International Center for Excellence in Malaria Research (ICEMR) to evaluate the effectiveness of the two interventions (alone and in combination) on malaria prevalence and transmission.
Objective: In this proposed implementation study, we propose to assess the impact of PBO nets and RTS,S vaccine on Plasmodium infection prevalence and transmission.
Study type and methodology: We will enroll children in a prospective cohort study in which the follow-up will be at the 2nd, 4th, and 6th month. We are selecting two health center catchment areas: one in which both RTS,S and PBO nets are available through the government health system and one in which there is no RTS,S vaccine available and standard long-lasting insecticide-treated nets (LLINS) have been distributed through the public section. At each visit, we will collect specimens to identify malaria infection and detect gametocyte infections. We will also collect and analyze mosquitoes from 100 households in both catchment areas to provide an entomological evidence of the force of infection. Children in households that are scheduled to receive both PBO nets and RTS,S vaccine will be compared to children in households that are not scheduled to receive either of these interventions.
- Being tested
- RTS,S/AS01 malaria vaccine, PBO bed nets
- Medical subject headings
- Malaria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RTS,S/AS01 malaria vaccineBiological
Also called RTS,S
Malaria vaccine: RTS,S is a subunit vaccine that includes a portion of the circumsporozoite protein (CSP) co-expressed with Hepatitis B surface antigen combined with an adjuvant. The Phase 3 trial of three doses administered to 5-17-month-olds confirmed moderate protection, with overall efficacy estimates of 50.4% against clinical malaria and 34.8% against severe malaria after three doses. Efficacy, which waned over time, was marginally improved by boosting at 18 months. The European Medicines Agency adopted a positive scientific opinion of the vaccine for use outside of the European Union. The World Health Organization has created the Malaria Vaccine Implementation Program (MVIP) and selected Malawi as one of the sites to explore the feasibility, efficacy and safety of RTS,S vaccination in the context of routine use.
PBO bed netsOther
PBO nets: The PBO nets represent a new formulation of insecticide-treated bed nets with a chemical synergist, piperonyl butoxide (PBO), designed to enhance the insecticidal effect of pyrethroids. They seem to be helpful in areas like Malawi where insecticide-resistance is increasing. PBO inhibits the enzyme that detoxifies the pyrethroid, allowing the pyrethroid to act on the mosquito. The impact of PBO net use was also detectable in key entomological measures including Anopheles density, sporozoite rate and entomological inoculation rates. Following these promising preliminary results in Tanzania, Malawi's National Malaria Control Program (NMCP) is piloting the use of PBO-nets iin one of our two study sites, presenting us with the opportunity to study the effectiveness of these nets in the context of real-world program setting
| Study group | Role | What they receive |
|---|---|---|
| Nyambi, rainy season | 250 children of age-eligible for RTS,S vaccine (7-18 months) 500 siblings (>18 months, < 10 years of age)
The duration of the cohort is six months. Receives: Biological: RTS,S/AS01 malaria vaccine; Other: PBO bed nets | |
| Nyambi, dry season | 250 children of age-eligible for RTS,S vaccine (7-18 months) 500 siblings (>18 months, < 10 years of age)
The duration of the cohort is six months. Receives: Biological: RTS,S/AS01 malaria vaccine; Other: PBO bed nets | |
| Kalembo, rainy season | 250 children of age-eligible for RTS,S vaccine (7-18 months) 500 siblings (>18 months, < 10 years of age) The duration of the cohort is six months. | |
| Kalembo, dry season | 250 children of age-eligible for RTS,S vaccine (7-18 months) 500 siblings (>18 months, < 10 years of age) The duration of the cohort is six months. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Malaria infection prevalence
Comparison of malaria infection prevalence in RTS/S cohorts compared to cohorts not exposed to RTS,S
Measured: 6 months/cohort, 4 cohorts in Phase 1
Anopheles species abundance
Comparison of Anopheles captured in households with PBO nets compared to household with conventional nets
Measured: 6 months/cohort, 4 cohorts in Phase 1
Secondary outcomes (5)
Gametocyte prevalence
Comparison of the prevalence of gametocytes (male and female) in cohorts exposed to RTS,S vs those not exposed
Measured: 6 months/cohort, 4 cohorts
Net usage
Comparison of nightly net usage in cohorts with PBO nets compared to cohorts with conventional nets
Measured: 6 months/cohort, 4 cohorts
Serological markers of immunity and exposure
Comparison of serological markers in cohorts exposed to RTS,S vs those not exposed to RTS,S
Measured: 6 months/cohort, 4 cohorts
Anopheles gravidity rates
Comparison of Anopheles gravidity rates in cohorts with PBO nets compared to cohorts with conventional nets
Measured: 6 months/cohort, 4 cohorts
Anopheles sporozoite rates
Comparison of Anopheles sporozoite rates in cohorts with PBO nets compared to cohorts with conventional nets
Measured: 6 months/cohort, 4 cohorts
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Mar 2020
- Study start4 Feb 2020
- Primary completion30 Jun 2021
- Study completion30 Jun 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Malaria, Malaria Vaccine, Insecticide-treated BednetsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 1,691 participants (actual)
Sponsor and investigators
- Lead sponsor
- Michigan State University
- Sponsor type
- University, hospital or other
- Collaborators
- Kamuzu University of Health Sciences, University of Maryland, Baltimore, Boston University, National Institute of Allergy and Infectious Diseases (NIAID)
- Responsible party
- Principal investigator, Terrie Taylor, Michigan State University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04327440
- Sponsor's protocol ID
- 00002662
- Other IDs
- 3U19AI089683-10S1
- Acronym
- RTSS/PBO
- Status last verified
- Sep 2025
- First submitted
- 27 Mar 2020
- Last updated
- 13 Jan 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Only de-identified data will be shared.
Study at a glance
From the registry record, last updated by the sponsor on 13 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Combined Effects of RTS,S Vaccination and PBO Nets on Malaria Infection and Transmission in Malawi
- ClinicalTrials.gov ID
- NCT04327440
- Acronym / sponsor ID
- RTSS/PBO / 00002662
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 1,691 participants (actual)
- Lead sponsor
- Michigan State UniversityUniversity, hospital or other
- Collaborators
- Kamuzu University of Health Sciences, University of Maryland, Baltimore, Boston University, National Institute of Allergy and Infectious Diseases (NIAID)
- Study start
- 4 Feb 2020 (actual)
- Primary completion
- 30 Jun 2021 (actual)
- Study completion
- 30 Jun 2021 (actual)
- First posted
- 31 Mar 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The overall goal of this study is to assess the impact of RTS,S (malaria) vaccination and PBO nets on malaria infection and transmission, independently and how they interact when they are introduced together.
The specific objectives for the study are as follows:
- To estimate the impact of PBO nets and RTS,S vaccine on Plasmodium infection prevalence and transmission, independently and how they interact when they are introduced together in Malawi (Phase 1).
- To assess the feasibility of evaluating the impact of RTS,S vaccine and PBO nets independently in a larger scale future study.
Detailed description
Introduction: The decline in malaria incidence has stalled globally and incidence is increasing in some high transmission settings of sub-Saharan Africa, including Malawi. The situation is worsening despite the scale-up of previously effective interventions, raising concerns that the impact of current malaria control and prevention strategies maybe compromised.
Problem: There is an urgent need for innovative approaches to malaria control and Malawi is currently positioned to assess two of the most promising new interventions. The Malawi Ministry of Health (MOH) is launching large scale projects to evaluate a new formulation of insecticide-treated bed nets with a chemical synergist, piperonyl butoxide (PBO), designed to enhance the insecticidal effect of pyrethroids and the new malaria vaccine RTS,S (RTS,S). In an effort to gain the most information from these, interventions Malawi's National Malaria Control Programme (NMCP) have invited the Malawi International Center for Excellence in Malaria Research (ICEMR) to evaluate the effectiveness of the two interventions (alone and in combination) on malaria prevalence and transmission.
Objective: In this proposed implementation study, we propose to assess the impact of PBO nets and RTS,S vaccine on Plasmodium infection prevalence and transmission.
Study type and methodology: We will enroll children in a prospective cohort study in which the follow-up will be at the 2nd, 4th, and 6th month. We are selecting two health center catchment areas: one in which both RTS,S and PBO nets are available through the government health system and one in which there is no RTS,S vaccine available and standard long-lasting insecticide-treated nets (LLINS) have been distributed through the public section. At each visit, we will collect specimens to identify malaria infection and detect gametocyte infections. We will also collect and analyze mosquitoes from 100 households in both catchment areas to provide an entomological evidence of the force of infection. Children in households that are scheduled to receive both PBO nets and RTS,S vaccine will be compared to children in households that are not scheduled to receive either of these interventions.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Nyambi, rainy season | – | Biological: RTS,S/AS01 malaria vaccine, Other: PBO bed nets250 children of age-eligible for RTS,S vaccine (7-18 months) 500 siblings (>18 months, < 10 years of age) The duration of the cohort is six months. |
| Nyambi, dry season | – | Biological: RTS,S/AS01 malaria vaccine, Other: PBO bed nets250 children of age-eligible for RTS,S vaccine (7-18 months) 500 siblings (>18 months, < 10 years of age) The duration of the cohort is six months. |
| Kalembo, rainy season | – | –250 children of age-eligible for RTS,S vaccine (7-18 months) 500 siblings (>18 months, < 10 years of age) The duration of the cohort is six months. |
| Kalembo, dry season | – | –250 children of age-eligible for RTS,S vaccine (7-18 months) 500 siblings (>18 months, < 10 years of age) The duration of the cohort is six months. |
Who may qualify
- Ages
- 7 months to 10 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
- Study population
- Children whose age is between 7 and 18 months, which indicates they could receive at least 3 RTS,S doses, will be eligible to participate. Following informed consent from parents/guardians, up to two children who are 18 months but ≤10 years of age, from the same household as the vaccine-eligible child, will also be enrolled. Only households whose families intend to stay in the area for at least six months and whose eligible children will also be expected to use an assigned health center for child vaccinations will be eligible to participate.
Key inclusion criteria (6 listed)
- Children aged 7 to 18 months of age (age-eligible for at least 3 doses of RTS,S doses) OR being one of not more than two children living in the household of an enrolled age-eligible child and being >18 mos and < 10 years of age.
- Not on cotrimoxazole prophylaxis for HIV infection
- Weight >5 kg
- Permanent residence of Health Centre (HC) catchment area
- Residence within 10 km from the HC
Key exclusion criteria (1 listed)
- Non-residents of the catchment area and visitors to the study area will be excluded because the study requires follow-up for at least 6 months and access to interventions such as conventional, PBO nets and malaria vaccination.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RTS,S/AS01 malaria vaccineAlso: RTS,SMalaria vaccine: RTS,S is a subunit vaccine that includes a portion of the circumsporozoite protein (CSP) co-expressed with Hepatitis B surface antigen combined with an adjuvant. The Phase 3 trial of three doses administered to 5-17-month-olds confirmed moderate protection, with overall efficacy estimates of 50.4% against clinical malaria and 34.8% against severe malaria after three doses. Efficacy, which waned over time, was marginally improved by boosting at 18 months. The European Medicines Agency adopted a positive scientific opinion of the vaccine for use outside of the European Union. The World Health Organization has created the Malaria Vaccine Implementation Program (MVIP) and selected Malawi as one of the sites to explore the feasibility, efficacy and safety of RTS,S vaccination in the context of routine use. | Biological | Nyambi, dry season, Nyambi, rainy season |
| PBO bed netsPBO nets: The PBO nets represent a new formulation of insecticide-treated bed nets with a chemical synergist, piperonyl butoxide (PBO), designed to enhance the insecticidal effect of pyrethroids. They seem to be helpful in areas like Malawi where insecticide-resistance is increasing. PBO inhibits the enzyme that detoxifies the pyrethroid, allowing the pyrethroid to act on the mosquito. The impact of PBO net use was also detectable in key entomological measures including Anopheles density, sporozoite rate and entomological inoculation rates. Following these promising preliminary results in Tanzania, Malawi's National Malaria Control Program (NMCP) is piloting the use of PBO-nets iin one of our two study sites, presenting us with the opportunity to study the effectiveness of these nets in the context of real-world program setting | Other | Nyambi, dry season, Nyambi, rainy season |
Primary outcome
Malaria infection prevalence
Time frame: 6 months/cohort, 4 cohorts in Phase 1
Comparison of malaria infection prevalence in RTS/S cohorts compared to cohorts not exposed to RTS,S
Anopheles species abundance
Time frame: 6 months/cohort, 4 cohorts in Phase 1
Comparison of Anopheles captured in households with PBO nets compared to household with conventional nets
5 secondary outcomes
Gametocyte prevalence
Time frame: 6 months/cohort, 4 cohorts
Net usage
Time frame: 6 months/cohort, 4 cohorts
Serological markers of immunity and exposure
Time frame: 6 months/cohort, 4 cohorts
Anopheles gravidity rates
Time frame: 6 months/cohort, 4 cohorts
Anopheles sporozoite rates
Time frame: 6 months/cohort, 4 cohorts
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jan 2026.
- Individual participant dataSharing planned: No. Only de-identified data will be shared.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Malaria, Malaria Vaccine, Insecticide-treated Bednets, run by Michigan State University at 1 site in Malawi.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Malawi. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Malaria infection prevalence (time frame: 6 months/cohort, 4 cohorts in Phase 1). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jan 2026.