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

José Diego Brito-Sousa ,Sheila Rodovalho,Judith Recht,Germana Bancone,Felipe Murta,Laila R A Barbosa,Quique Bassat,Brenda K A Souza,Emanuelle L Silva,Gonzalo J Domingo,Thaliê Cavalcante Santos ,Leonardo Lincoln Gomes Marques ,Ana Ruth Lima Arcanjo ,André Machado Siqueira ,Maxwell Oliveira Mendes ,Vanderson De Souza Sampaio ,Talita Suelem Bastos Batista ,Theresa Helissa Nakagawa ,Marcelo Augusto Mota Brito ,Djane Clarys Baía-Da-Silva ,Gisely Cardoso De Melo ,Alicia Patrine Cacau Santos ,Alexandre Vilhena Silva-Neto ,Sheila Vítor-Silva ,Erick Frota Gomes Figueiredo ,Marly Marques De Melo ,Marcus Lacerda

doi:10.1371/journal.pntd.0009415

Abstract

BackgroundGlucose-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 findingsThe 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/SignificanceG6PD 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.

Highlights

Glucose 6-phosphate dehydrogenase deficiency (G6PDd) has greatly impacted the treatment of Plasmodium vivax malaria because of the red blood cell destruction in what is known as hemolysis
This study revealed that, G6PDd was not previously known by most of the healthcare workers, they were able to perform the test after a single training session
The radical cure for Plasmodium vivax malaria is achieved by combination therapy using blood schizontocidal agents along with an 8-aminoquinoline drug, of which primaquine (PQ) is the most used worldwide

Summary

Introduction

The radical cure for Plasmodium vivax malaria is achieved by combination therapy using blood schizontocidal agents along with an 8-aminoquinoline drug, of which primaquine (PQ) is the most used worldwide. The use of PQ is associated with acute hemolytic anemia (AHA) in a dose-dependent manner in patients presenting glucose-6-phosphate dehydrogenase (G6PD) deficiency (G6PDd); G6PDd is an X-linked genetic condition estimated to affect 8% of the world’s population living in malaria endemic areas [1]. Glucose-6-phosphate dehydrogenase (G6PD) deficiency greatly hinders Plasmodium vivax malaria radical cure and further elimination due to 8-aminoquinolines-associated hemolysis. 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

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