Real-life implementation of a G6PD deficiency screening qualitative test into routine vivax malaria diagnostic units in the Brazilian Amazon (SAFEPRIM study)

Abstract

Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency greatly hinders Plasmodium vivax malaria radical cure and further elimination due to 8-aminoquinolines-associated hemolysis. Although the deleterious health effects of primaquine in G6PD deficient individuals have been known for over 50 years, G6PD testing is not routinely performed before primaquine treatment in most P. vivax endemic areas.

Method/principal findings: The qualitative CareStart G6PD screening test was implemented in 12 malaria treatment units (MTUs) in the municipality of Rio Preto da Eva, Western Brazilian Amazon, a malaria endemic area, between February 2019 and early January 2020. Training materials were developed and validated; evaluations were conducted on the effectiveness of training health care professionals (HCPs) to perform the test, the interpretation and reliability of routine testing performed by HCPs, and perceptions of HCPs and patients. Most HCPs were unaware of G6PD deficiency and primaquine-related adverse effects. Most of 110 HCPs trained (86/110, 78%) were able to correctly perform the G6PD test after a single 4-hour training session. The test performed by HCPs during implementation showed 100.0% (4/4) sensitivity and 68.1% (62/91) specificity in identifying G6PD deficient patients as compared to a point-of-care quantitative test (Standard G6PD).

Conclusions/significance: G6PD screening using the qualitative CareStart G6PD test performed by HCPs in MTUs of an endemic area showed high sensitivity and concerning low specificity. The amount of false G6PD deficiency detected led to substantial loss of opportunities for radical cure.

Fig 1. Study location and malaria treatment units (MTU).

Rio Preto da Eva is located 78 km from Manaus, capital of the State of Amazonas, Western Brazilian Amazon. The test was implemented in 5 urban (including the local hospital, black sign and black circle, respectively) and 7 rural health posts (filled grey circles). This map was created using the base from the Brazilian Institute of Geography and Statistics (https://portaldemapas.ibge.gov.br/portal.php#homepage).

Fig 2. Timeline of events.

Timeline of events is shown consisting of three phases: 1) pre-training (before any study intervention, yellow), pre-implementation (after training but before implementation, green), and implementation period (actual implementation of the test, blue). Each M corresponds to a month of implementation, where M1 is March 2019, M10 is December 2019, and M11 is early January 2020.

Fig 3. G6PD activity quantitation and genotyping of G6PD RDT normal and deficient samples.

G6PD activity measured by point-of-care quantification (Y axis) is shown for CareStart RDT normal and deficient samples (X axis left and right, respectively) in Rio Preto da Eva, Brazil. G6PD African A-, African A+ and wild type variants are indicated by black, red and green colors, respectively. Circles below the red-dashed line (cut-off point 4.0 UI/g Hb) are considered G6PD deficient (<30%) as per quantitative test results.

Fig 4. Patient acceptability of the test.

Blue and red boxes show reasons for trusting and barriers to the test, respectively.