Biological Mechanisms in Afebrile P. Falciparum Malaria (AsintMal)

August 29, 2023 updated by: Alfredo Mayor

Unravelling Disease Tolerance and Host Resistance in Afebrile P. Falciparum Infections: a Prospective Study in Mozambican Adults

This project aims to disentangle the role of host immune resistance and disease tolerance in afebrile malaria infections, with the goal of guiding context-adapted tactics to target this hidden reservoir, as well as to develop new approaches to clear malaria infection and reduce its severity through host-directed therapies.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Asymptomatic Plasmodium falciparum (Pf) infections debilitate the health of affected population while representing a hidden source of parasite transmission that can compromise elimination efforts. The lack of consensus on the best strategy to deal with this asymptomatic reservoir is partly due to the poor knowledge on the biological mechanisms underlying these subclinical infections. Preliminary results in Mozambique show that afebrile adults with a Pf infection detected by rapid diagnostic tests can progress to fever (10%), clear the infection (20%) and stabilize at low-density (50%) or high-density (20%) parasitemias. The study hypothesis is that these four main trajectories are driven by antibodies against Pf variant antigens, codified by the var gene family and expressed on the surface of infected erythrocytes, which would clear the infection unless the parasites develop immune evasion mechanisms, and by tolerance factors that minimize parasite-induced pathology and sustains host homeostasis.With the overarching goal of identifying key biological factors sustaining afebrile malaria infections, this project will establish a cohort of afebrile Mozambican adults followed during one month to identify subjects who can reduce pathogen load and eventually clear the infection, those who maintain infections at high-density and afebrile levels (tolerant), and those who fail to establish disease tolerance and progress to fever. Circulating and overall parasite biomass will be quantified, and new infections will be identified during follow-up using next-generation sequencing. Clinical samples from individuals with low and high parasite densities will be used to test whether parasitological trajectories of afebrile Pf infections correlate with host antibody immunity against erythrocyte surface antigens and the transcription of Pf var genes involved in cytoadhesion and immune evasion. Cytometry by time of flight and global mass spectrometry will be applied on clinical samples from afebrile individuals with high parasite densities (tolerant) and those progressing to fever (non-tolerant) to identify leukocyte populations and metabolic pathways involved in the regulation of inflammation, tissue damage and normoglycemia that support host-parasite relationships at afebrile levels. The expected outcome of this project is the identification of key molecular drivers of afebrile Pf infections for a better understanding of the relevance of these infections in different transmission setting which may require context-specific control approaches, as well as for the development of new tools to achieve sterilizing immunity and enhance disease tolerance.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
475

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • Mozambique
      • Manhiça, Mozambique, 1929
        • Fundação Manhiça/Manhiça Health Research Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 60 years (Adult)

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

Healthy individuals (temperature below 37.5ºC) with a P. falciprum infection confirmed by RDT and microscopy

Description

Inclusion Criteria:

  • Age ≥ 18 years and ≤60 years
  • A positive RDT and microscopy for P. falciparum
  • Axillary temperature < 37.5ºC without history of fever during the last 24h
  • No danger signals for severe malaria (Impaired consciousness, respiratory distress, multiple convulsions, prostration, shock, abnormal bleeding, jaundice)
  • Ability and willingness to comply with the study protocol for the duration of the study and to comply with the study visit schedule; and
  • Signed informed consent after explaining the purpose of the study

Exclusion Criteria:

  • Age <18 years or >60 years
  • Axillary temperature ≥37.5ºC
  • Reported pregnancy
  • Presence of any sign/symptom of malaria (Vomiting, diarrhea, weakness, dizziness, fainting, itching, urticarial)
  • Presence of any other co-existing clinical condition that would not allow the individual to be considered a "healthy" afebrile carrier
  • Having received antimalarial medication in the preceding 30 days.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Proportion of individuals developing fever
Time Frame: 1 month
Development of axilary temperature higher or equal than 37.5ºC
1 month

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Proportion of individuals clearing the infection
Time Frame: 1 month
Clearance of parasite infection as detected by qPCR
1 month
Proportion of individuals maintaining infections without fever
Time Frame: 1 month
Confirmed P. falciparum ifection at day 28 by qPCR
1 month

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Alfredo Mayor

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
University of Florida
Stanford University
Centro de Investigacao em Saude de Manhica

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 1, 2020

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 31, 2021

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 31, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 4, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 4, 2020

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 9, 2020

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 1, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 29, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 1R01AI150521 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Falciparum Malaria

Clinical Trials on No intervention

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings