Abbott NxTekTM Malaria RDT WHO Prequalification Study

Clinical Performance of NxTekTM Malaria P.f Plus Rapid Diagnostic Test Device and NxTekTM Malaria P.f/P.v Plus Rapid Diagnostic Test Device for the Detection of Plasmodium Infections in Patients With Symptoms Suggestive of Malaria for WHO Prequalification

Since their introduction in the late 90's, rapid diagnostic tests (RDTs) have dramatically improved our ability to control malaria but proved insufficient to support elimination efforts because of their limited sensitivity, especially for P. vivax. In addition, the spread of P. falciparum parasites lacking hrp2 gene jeopardizes the long-term use of P. falciparum-specific HRP2-based RDTs. A partnership between Abbott, FIND, PATH, and the Bill and Melinda Gates Foundation (BMGF) is addressing these limitations by developing two novel malaria RDTs with improved pLDH detection: a P. falciparum-specific test targeting both the HRP2 and PfLDH antigens on a single test line (NxTekTM Malaria P.f plus Rapid Diagnostic Test Device), and a P. falciparum/P. vivax combo test additionally targeting the PvLDH antigen on a second test line (NxTekTM Malaria P.f/P.v. plus Rapid Diagnostic Test Device).

These new combo tests with improved pLDH detection may provide added value compared to currently available malaria RDTs, especially in settings where current tests prove to be insufficient due to hrp2 deletion or high burden of P. vivax malaria.

Abbott, PATH, and FIND will conduct a prospective evaluation of NxTekTM Malaria P.f plus and NxTekTM Malaria P.f/P.v plus RDTs in malaria-endemic countries to assess their clinical performance for detection of malaria and usability in their intended-use settings. This is in support of a submission for WHO Prequalification.The purpose of this synopsis is to describe key points of alignment in study design and conduct across the portfolio of studies.

Study Overview

• Status: Completed
• Conditions: Malaria; Diagnoses Disease; RDT
• Intervention / Treatment: Diagnostic test: Rapid Diagnostic Test

Detailed Description

Malaria continues to create a major health burden in the tropics especially in Africa. Introduction of Artemisinin-based combination therapy (ACT) has dramatically improved the outcomes of morbidity and mortality of malaria cases. Introduction of RDTs as well dramatically influenced cases detection hence treatment. The situation in Sudan is not different from the general picture in all Africa and witness great reduction of deaths from malaria since the introduction of ACT in 2005. The national protocol depends now on Giemsa stained slides microcopy or certified RDTs for diagnosis and ACT as first and second line of treatment.

Recommendation by World Health Organization (WHO) on parasitological confirmation of malaria cases by microscopy or rapid diagnostic tests (RDTs) before treatment increased the use and availability of RDTs worldwide.

Rapid diagnostic tests, since their introduction in the late 90's, have dramatically improved our ability to control malaria. Most RDTs are based on histidine-rich protein 2 (PfHRP2) or lactate dehydrogenase (pLDH), which are present in Plasmodium falciparum only and all human-infecting Plasmodium species respectively. However, the gradual spread of hrp2/hrp3-deleted mutants in several endemic countries in South America, Asia and Africa exerts a substantial potential impact on the utility of HRP2-based RDTs for case management in these settings.

Plasmodium lactate dehydrogenase (pLDH), on the other hand, appears as a good alternative to HRP2 as it is an essential protein expressed by all human-infecting Plasmodium species; however, pLDH-based RDTs were shown to perform poorly at low parasitaemia, which is common among patients infected with P. vivax, P. malariae and P. ovale species as well as in asymptomatic infections. Therefore, it is less preferred in endemic-countries. In these settings, malaria microscopy holds its reign as the standard of reference thanks to its low direct cost and ability to detect, quantify, and differentiate malaria parasites. However, it is also labour-intensive, time-consuming and expertise-demanding.

With the aim of addressing these limitations, Abbott has developed novel malaria RDTs, namely; NxTekTM Malaria Pf/Pv Plus and NxTekTM Malaria Pf Plus. These may provide added value compared to currently available malaria RDTs, especially in settings where current tests prove to be insufficient due to hrp2 deletion or high burden of P. vivax malaria.

• Study Type: Observational
• Enrollment (Actual): 4563

Contacts and Locations

Study Locations

• Indonesia
  • Jakarta, Indonesia, 12870
    • Exeins Health Institute
• Peru
  • Lima, Peru, 15102
    • Universidad Peruana Cayetano Heredia
• Sudan
  • Khartoum, Sudan
    • Institute of Endemic Diseases, Medical Campus

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with symptoms suggestive of malaria seeking clinical care in health facilities. By default, all such patients will be assessed for eligibility and, if appropriate, recruited in the study.

Description

Inclusion Criteria:

• Aged 5 years old or older
• Presenting at the study site with fever or a history of fever during the preceding 48 hours
• Freely agreeing to participate by providing informed consent (and assent, if applicable)

Exclusion Criteria:

• Presence of symptoms and signs of severe illness and/or central nervous system infections as defined by WHO guidelines

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Point estimates of NxTekTM Malaria Pf Plus	Point estimates of diagnostic accuracy characteristics (sensitivity, specificity, NPV, PPV) with 95% confidence intervals for NxTekTM Malaria Pf Plus using the reference test (nPCR) as standard of truth for the detection of P. falciparum infections in patients with symptoms suggestive of malaria.	8 Months
Point estimates of NxTekTM Malaria Pf/Pv Plus	Point estimates of diagnostic accuracy characteristics (sensitivity, specificity, NPV, PPV) with 95% confidence intervals for NxTekTM Malaria Pf/Pv Plus using the reference test as standard of truth for the detection of P. falciparum and P.vivax infections in patients with symptoms suggestive of malaria.	8 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Point estimates of comparator tests	Point estimates of diagnostic accuracy characteristics (sensitivity, specificity, NPV, PPV) with 95% confidence intervals of comparator tests using the reference test as standard of truth for the detection of P. falciparum and, P.vivax infections in patients with symptoms suggestive of malaria	8 months
Point estimates of index tests	Point estimates of diagnostic accuracy characteristics with 95% confidence intervals (sensitivity, specificity, NPV, PPV) of the index tests for the detection of P. falciparum infections with hrp2 and/or hrp3 deletions in patients with symptoms suggestive of malaria.	8 months
User ability to read and interpret test	2.4 Percent of end users who can accurately interpret the investigational device result output.	8 months

Collaborators and Investigators

• Sponsor: Foundation for Innovative New Diagnostics, Switzerland
• Collaborators: University of Khartoum; Universidad Peruana Cayetano Heredia; Eijkman Institute for Molecular Biology

Study record dates

Study Major Dates

• Study Start (Actual): June 30, 2022
• Primary Completion (Actual): April 30, 2023
• Study Completion (Actual): July 30, 2023

Study Registration Dates

• First Submitted: June 30, 2022
• First Submitted That Met QC Criteria: June 30, 2022
• First Posted (Actual): July 6, 2022

Study Record Updates

• Last Update Posted (Actual): October 13, 2023
• Last Update Submitted That Met QC Criteria: October 12, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Malaria, Diagnostics, RDT
• Additional Relevant MeSH Terms: Infections; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Malaria
• Other Study ID Numbers: MA016 Abbott

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No