Evaluating the Clinical Performance and Usability of Novel Malaria RDTs in Brazil

Evaluating the Clinical Performance and Usability of Novel Malaria Rapid Diagnostic Tests (RDTs) for the Detection of Plasmodium Malaria Infections in Brazil

Prospective cross-sectional diagnostic accuracy study with 1,000 patient participants and 30 lay provider/health care worker participants. The patient participant population will be recruited at clinics. At the point of care, study staff will collect capillary blood samples and conduct malaria microscopy (both the standard of care and study specific research-grade microscopy) and two index tests: the NxTek™ Malaria P.f plus Rapid Diagnostic Test (RDT) and the NxTek™ Malaria P.f/P.v RDT. Venous blood will be collected and transferred to the laboratory where the reference PCR assay and three comparator RDTs will be run. The index RDTs will also be repeated in the laboratory. All clinical management of study participants will follow the standard of care for malaria diagnosis in Brazil and will be based on the standard microscopy result. Confirmatory testing may also be conducted, such as typing and sequencing of Plasmodium genes and antigens of interest, including but not limited to HRP2, HRP3, and pLDH as well as the human inflammatory response marker CRP.

The lay provider/health worker participants will include intended users of the index tests. They will be surveyed to assess index test usability through a questionnaire to assess label and packaging comprehension as well as results interpretation.

Primary Objectives

1.1 To assess the sensitivity, specificity and, when applicable, positive and negative predicting values (PPV and NPV) [altogether referred to hereafter as "diagnostic accuracy"] of NxTek™ Malaria Pf Plus in intended use settings for detecting P. falciparum infections in capillary whole blood samples collected prospectively from patients with symptoms suggestive of malaria.

1.2 To assess the diagnostic accuracy of NxTek™ Malaria Pf/Pv Plus in intended use settings for detecting P. falciparum and P. vivax infections in capillary whole blood samples collected prospectively from patients with symptoms suggestive of malaria.

Secondary Objectives

2.1 To assess the diagnostic accuracy of the study comparator tests in intended use settings for detecting P. falciparum and P. vivax infections in venous whole blood samples collected prospectively from patients with symptoms suggestive of malaria.

1.3 To determine the frequency of P. falciparum infections containing HRP2 and/or HRP3 mutations and assess the impact of those on HRP2-based RDT diagnostic accuracy.

1.4 To assess the comprehension of the test packaging and labeling among intended users (trained lay providers and trained health care workers).

1.5 To assess the ability to read and interpret the test result outputs among intended users (trained lay providers and trained health care workers).

Inclusion Criteria (diagnostic accuracy):

• Aged 2 years of age 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, as applicable)

Exclusion Criteria (diagnostic accuracy):

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

Inclusion Criteria (usability):

• Aged 18 years of age or older
• Provides malaria case management at the study site
• Considered an intended user of the index tests (lay user or healthcare worker)
• Freely agreeing to participate by providing informed consent

Exclusion Criteria (usability):

None