A research team with members from the Juan Ciudad NGO Foundation, ISGlobal, Monrovia Hospital, and the Liberian Drug Regulatory Authority are developing DiagLib, a research activity on malaria diagnosis that will involve the recruitment of 3,850 patients, including pregnant women.
Research and development of preventive and therapeutic interventions for emerging pathogens has been difficult to sustain in the past once outbreaks ended. In Liberia, much of the Ebola research ended when the outbreak faded in 2016, although if funding had been maintained, a larger number of projects to develop Ebola vaccines and other therapies could have been carried out.
Therefore, a major challenge is maintaining the continuity of studies and preparing research sites, including infrastructure and staffing capabilities, for future clinical trials that could lead to an effective vaccine or treatment for infectious diseases prevalent in Liberia.
Dr. Cristina Muñoz, coordinator of the IGORCADIA research project, with a laboratory worker at Saint Joseph's Catholic Hospital in Monrovia.
In preparation for future trials in emerging epidemics, Liberia must ensure that cases with suspected or confirmed infections have access to the most accurate diagnostics. Furthermore, healthcare providers must have access to the most reliable diagnostics to avoid interrupting their clinical activities and reduce the risk of patient burnout and the development of clinical complications, such as opportunistic infections.
The project IGORCADIA -which by its translated acronym means Improving governance and research capabilities in infectious disease diagnostics at the Liberia Drugs and Health Products Regulatory Authority (LMHRA))â aims to develop this organization's capabilities to improve the future use of diagnostics and everything related to their research. Specifically, the project will result in improved training in good clinical practices, good laboratory practices, fundamentals of medical ethics, and diagnostic research.
IGORCADIA launched in December 2017 and involves four participating institutions. It is led by the Barcelona Institute for Global Health (ISGlobal) in collaboration with the Juan Ciudad NGO Foundation, LMHRA, and Saint Joseph Catholic Hospital in Monrovia, where all activities are carried out. This project is funded by the European Union through the Horizon 2020 research program.
A Monrovia hospital worker during training with materials from the IGORCADIA project.
Three main areas
IGORCADIA's activities will have an impact in three main areas:
- strengthening the capacity of LMHRA as a government organization to regulate in vitro diagnostic medical devices.
- the capacity of the Hospital laboratory St. Joseph Catholic University of Monrovia as the LMHRA reference laboratory and networking with other institutions involved in research and development of investigational drugs and vaccines
- education and commitment of the community.
Collaborative research
A research team made up of members of the four institutions involved in IGORCADIA have proposed the research activity âMalaria Diagnosis at St. Joseph's Hospital in Monroviaâ (DiagLib), highlighting ISGlobal, an organization with extensive experience in malaria research.
For this reason, this hospital has already conducted previous research with ISGlobal that evaluated the prevalence of malaria in Liberian pregnant women attending prenatal clinics, detecting that younger and first-time mothers had a higher risk of infection by parasites of the genus Plasmodium, which causes the disease.
Now, with this new DiagLib study, we hope to provide relevant information on the use of diagnostics at a referral hospital in Liberia, such as San José Hospital, in addition to the prevalence of Pfhrp2 deletions that can lead to erroneous diagnoses and false negative results, with the adverse consequences this can have for patients.
Cristina Muñoz at a presentation to the staff of St. Joseph Catholic Hospital in Monrovia.
As explained Cristina Muñoz, coordinator of IGORACIA and researcher at IsGlobalWith the launch of DiagLib, "we will strengthen the laboratory's capabilities at St. Joseph's Catholic Hospital in Monrovia and establish it as a reference laboratory partner for LMHRA. To ensure a smooth DiagLib run, the laboratory has been upgraded with equipment, reagents, and other consumables."
Furthermore, the DiagLib-IGORCADIA research is expected to contribute to restore healthcare capabilities, management, and research in a country that has suffered greatly from the recent Ebola outbreak. "Importantly, we hope it will help neighboring communities regain confidence in the health system, as well as their participation in clinical trials aimed at finding vaccines or treatments for emerging infectious diseases that pose a threat to the region."
We tell you about the DiagLib methodology
DiagLib will analyze malaria infection in blood samples taken from individuals with fever or a history of fever within the previous 24 hours, as well as from pregnant women at their first prenatal care visit, using molecular and serological approaches.
Study design: Patients with fever (temperature â„37.5°C) or a history of fever in the past 24 hours, and pregnant women (irrespective of fever status) at their first antenatal visit will be recruited after providing written informed consent for the study and will be asked to provide a finger-prick blood sample on filter papers. Study participants will be screened for malaria infection using an HRP2-based RDT and microscopy. Blood on the filter papers will be analyzed by qPCR for the presence of malaria parasites. To explore perceptions on biobanking of biological samples for future studies on in vitro diagnostics, stakeholders and community members will be contacted following a structured interview.
Sample size: A sample size of 385 qPCR-positive malaria cases is needed to estimate a sensitivity of 80% with an accuracy of +/- 0.04 (4%) at a confidence level of 95%. Assuming a total of 40 patients with malaria signs/symptoms (10% of whom are expected to be qPCR-positive), 3,850 patients need to be recruited over a 6-month period. Recruiting 385 pregnant women at the first antenatal visit would allow us to detect a conservative P. falciparum prevalence of 50% with an accuracy of 5% and a confidence level of 95%.
Study period: Once ethics approval is received, this study will last 12 months. According to the established schedule, the project is now expected to begin recruiting and sampling participants from April to September 2019 (although this period may be extended depending on the number of participants recruited per month). The analysis of findings, preparation of results, and dissemination to communities are planned for September to November of this year.
Molecular analysis: DNA will be extracted from one half of the filter paper using the Chelex method. An ABI PRISM 7500 HT real-time system (Applied Biosystems) will be used to amplify DNA templates from purified parasites, using a qPCR method described previously. If the presence of Pf is confirmed by qPCR, a standard nested PCR will be performed to amplify the k13, hrp2, and hrp3 genes. Deletions in hrp2 and hrp3 will be considered if k13 is positive but hrp2 or hrp3 PCR is negative.
Ethical considerations: Written informed consent will be requested from adults, while in the case of minors, caregiver consent and the minor's permission will be requested. Project activities began after obtaining ethical clearance from the Liberia Ethics Review Committee and the Ethics Review Committee of the Hospital ClĂnic de Barcelona.
Text source: Overview Malaria Diagnostic Research in the SJCH (DiagLib) article by Cristina Muñoz within the framework of IGORCADIA.
Translation and editing: Adriana Castro, Head of Communications at the Juan Ciudad NGO Foundation.
Photos: Adriana Castro.
More information: www.igorcadia.org
Project: Improving the governance and research capacity of the Liberia Drug and Health Products Regulatory Authority (IGORCADIA) in infectious disease diagnostics.
Project: Improved Governance and Research Capacities in Diagnostics for Infectious Diseases of the Liberian Medicines and Health Products Regulatory Authority
The EDCTP2 program is supported under Horizon 2020, the European Union's Framework Program for Research and Innovation
