Assessing the Operational Feasibility of Integrating Point-of-Care G6PD Testing into Plasmodium vivax Malaria Management in Vietnam.

Plasmodium vivax cases represent more than 50% of a diminishing malaria case load in Vietnam. Safe and effective radical cure strategies could support malaria elimination by 2030. This study investigated the operational feasibility of introducing point-of-care quantitative glucose-6-phosphate dehydrogenase (G6PD) testing into malaria case management practices. A prospective interventional study was conducted at nine district hospitals and commune health stations in Binh Phuoc and Gia Lai provinces in Vietnam over the period of October 2020 to October 2021. The STANDARD™ G6PD Test (SD Biosensor, Seoul, Republic of Korea) was incorporated to inform P. vivax case management. Case management data and patient and health care provider (HCP) perspectives, as well as detailed cost data were collected. The G6PD test results were interpreted correctly by HCP and the treatment algorithm was adhered to for the majority of patients. One HCP consistently ran the test incorrectly, which was identified during the monitoring and resulted in provision of refresher training and updating of training materials and patient retesting. There was wide acceptability of the intervention among patients and HCP albeit with opportunities to improve the counseling materials. Increasing the number of facilities to which the test was deployed and decreases in the malaria cases resulted in higher per patient cost for incorporating G6PD testing into the system. Commodity costs can be reduced by using the 10-unit kits compared to the 25 unit kits, particularly when the case loads are low. These results demonstrate intervention feasibility while also highlighting specific challenges for a country approaching malaria elimination.

Co-Occurring Hemolysis and Methemoglobinemia After COVID-19 Infection in Patient With G6PD Deficiency.

Hemolytic anemia and methemoglobinemia are known complications in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. They can be elicited by various oxidative stressors. Here we report a case of an adult with the first episode of G6PD deficiency associated hemolysis and methemoglobinemia after acquiring COVID-19 infection, who had no recent exposure to oxidative drugs or fava beans. A 52-year-old gentleman known to have myocardial bridging on aspirin and beta-blocker, with no other medical illnesses, developed anemia symptoms, jaundice, and hypoxia after contracting COVID-19 infection. Further laboratory work revealed non-immune hemolytic anemia, methemoglobinemia, and a positive G6PD screen test. He was treated conservatively with a blood transfusion, and his oxygen saturation improved thereafter. With the widespread COVID-19 infection and its morbidity worldwide, it is crucial to consider methemoglobinemia in the differential diagnosis of hypoxia. Testing for G6PD is an essential next step in such cases, as starting methylene blue in G6PD deficiency can worsen hemolysis. Apart from COVID-19, there is no other identified trigger for the acute event in this patient. It is not known whether COVID-19 infection alone is enough to result in G6PD deficiency-associated hemolysis and methemoglobinemia simultaneously.

G6PD deficiency-does it alter the course of COVID-19 infections?

Despite the existence of well-founded data around the relationship between reactive oxygen species (ROS) and glucose-6-phosphate dehydrogenase (G6PD), current research around G6PD-deficient patients with viral infections, and limitations as a result of their condition, are inadequate. Here, we analyze existing data around immunological risks, complications, and consequences of this disease, particularly in relation to COVID-19 infections and treatment. The relationship between G6PD deficiency and elevated ROS leading to increased viral load suggests that these patients may confer heightened infectivity. Additionally, worsened prognoses and more severe complications of infection may be realized in class I G6PD-deficient individuals. Though more research is demanded on the topic, preliminary studies suggest that antioxidative therapy which reduces ROS levels in these patients could prove beneficial in the treatment of viral infections in G6PD-deficient individuals.

Infections in G6PD-Deficient Hospitalized Patients-Prevalence, Risk Factors, and Related Mortality.

G6PD deficiency is a genetic disease that weakens the immune system and renders affected individuals susceptible to infections. In the Sultanate of Oman resides a high number of recorded G6PD cases due to widespread consanguineous marriage, which may reach 25% of the population. We studied the infection patterns and risk factors for mortality to provide antimicrobial stewardship recommendations for these patients. After obtaining ethical approval, a registry of recorded cases was consulted retrospectively to include G6PD-deficient adult patients admitted to Suhar hospital over 5 years with microbiologically confirmed infections. Patient demographics, health-related information, infection causes, treatment, and clinical outcomes were studied. Data were analyzed to describe infection patterns and risk factors. Several variables, including underlying comorbidities and hospitalization details, such as length of stay, admission to critical care unit, blood transfusion, or exposure to an invasive procedure, were statistically associated with the acquisition of multidrug-resistant and hospital-acquired infections. Meanwhile, these infections were associated with a high mortality rate (28%), significantly associated with the patient's health status and earlier exposure to antimicrobial treatment due to previous bacterial infection. The high prevalence of G6PD deficiency among the Omani population should alert practitioners to take early action when dealing with such cases during infection that requires hospitalization. Strict infection control measures, Gram-negative empiric coverage, hospital discharge as early as possible, and potent targeted antimicrobial therapy in this patient population can ameliorate the treatment outcomes and should be emphasized by the antimicrobial stewardship team.

G6PD deficiency: imbalance of functional dichotomy contributing to the severity of COVID-19.

Human COVID-19 has affected more than 491 million people worldwide. It has caused over 6.1 million deaths and has especially perpetrated a high number of casualties among the elderly and those with comorbid illnesses. COVID-19 triggers a pro-oxidant response, leading to the production of reactive oxygen species (ROS) as a common innate defense mechanism. However, ROS are regulated by a key enzyme called G6PD via the production of reduced nicotinamide adenine dinucleotide phosphate (NADPH), which controls the generation and removal of ROS in a tissue-specific manner. Therefore, a deficiency of G6PD can lead to the dysregulation of ROS, which causes a severe inflammatory response in COVID-19 patients. This report highlights the G6PD dichotomy in the regulation of ROS and inflammatory responses, as well as its deficiency in severity among COVID-19 patients.

Occurrence of Methemoglobinemia due to COVID-19: A Case Report.

Methemoglobinemia (MetHb) is a rare, life-threatening condition that occurs when the body is exposed to oxidative stress. It is typically corrected through the glucose-6-phosphate dehydrogenase (G6PD)-dependent shunt. G6PD deficiency is the most common enzymatic deficiency worldwide. This genetic disorder makes patients susceptible to oxidative stress and reduces the expected life span of erythrocytes (red blood cells (RBCs)) among other cells. G6PD deficiency is asymptomatic in most cases unless exogenous stressors are introduced, whether they are dietary, iatrogenic, or infections, such as the highly transmissible serotype of coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We report a case of an 11-year-old male with known insulin-dependent diabetes mellitus (IDDM) and glucose-6-phosphate dehydrogenase (G6PD) deficiency, who was found to develop methemoglobinemia after being infected by the SARS-CoV-2 virus. The direct effects of COVID-19 on children were reported to be lower than on adults. However, the effects of COVID-19 on children with comorbidities, such as G6PD deficiency in our patient, are understood only to a minimal extent. Moreover, identifying cases of G6PD deficiency prior to initiating treatment with methylene blue, hydroxychloroquine (HCQ), or other contraindicated agents is essential to prevent further deterioration in symptoms.

Hemolytic Anemia Complicating COVID-19 Infection.

Coronavirus disease 2019 (COVID-19) has been associated with a spectrum of reported hematological complications ranging from immune cytopenias to thromboembolic manifestations of coagulopathy. Moreover, there have been documented cases of hemolytic anemia associated with COVID-19 infection which have been mainly attributed to development of autoantibodies. We report a case of an African-American patient who presented with hemolytic anemia in the second week after his COVID-19 diagnosis. Throughout this report, we explore the potential immune and non-immune etiologies that contributed to the patient's hemolytic anemia in the setting of COVID-19 infection guided by a review of literature.

Glucose-6-phosphate dehydrogenase deficiency and hydroxychloroquine in the COVID-19 era: a mini review.

The coronavirus disease 2019 (COVID-19) is until today a global health emergency. In an immense effort, effective drugs against COVID-19 are searched and intensive researches on possible repurposing of antiviral agents are performed. Since chloroquine (CQ) and hydroxychloroquine (HCQ) have shown in vitro anti- COVID-19 activities, the potential effect of CQ/HCQ to treat and/or prevent COVID-19 infection has caused global attention. However, concern regarding possible hemolysis in G6PD-deficient COVID-19 patients exists and for this reason, the association between HCQ and G6PD deficiency (G6PDD) is back in the limelight. This study aims to answer the question raised by Mastroianni et al. "Hydroxychloroquine: Culprit or Innocent Bystander in G6PD-Deficient Patients with COVID-19?", reporting all cases of HCQ in G6PD deficient COVID-19 patients published on PubMed (pubmed.ncbi.nlm.nih.gov), in addition to the Mastroianni's patient. In our opinion, after an accurate revision of these cases and responding the question raised by Mastroianni et al., we believe that it is difficult to reach a final verdict about the definitive role of HCQ in these patients. The COVID-19 pandemic has reopened attention on HCQ use and G6PDD. G6PD status is extremely important in modulating the level of reactive oxygen species and many cellular immune responses such as enhanced production of the pro-inflammatory cytokine and inflammasome activation. Since these processes are involved in COVID-19 infection, acute hemolytic anemia, a severe complication of the G6PDD, can occur in these patients. In this context, the role of HCQ, usually effective, safe, and well tolerated in G6PD deficient patients, must be redefined in these patients with COVID-19.As consequence, answering the question: "Hydroxychloroquine: Culprit or Innocent Bystander in G6PD-Deficient Patients with COVID-19?", we state that it is risky to believe that HCQ may be an "innocent bystander" in G6PD-deficient COVID-19 patients.

Hydroxychloroquine in a G6PD-Deficient Patient with COVID-19 Complicated by Haemolytic Anaemia: Culprit or Innocent Bystander?

Hydroxychloroquine has been used worldwide as a first-line treatment for patients hospitalized with COVID-19. Little is known about COVID-19 and its effects on patients with congenital red blood cell disorders. We report a case of haemolytic anaemia in a 32-year-old patient and a fortuitous highlighting of G6PD deficiency. We reviewed the literature to assess the risk of hydroxychloroquine use in this context. LEARNING POINTS: A rapid drop in haemoglobin in COVID-19 patients should alert physicians to test for haemolytic anaemia and enzymopathies.Our review of the literature shows that use of hydroxychloroquine is safe in G6PD-deficient patients.

A case report of serious haemolysis in a glucose-6-phosphate dehydrogenase-deficient COVID-19 patient receiving hydroxychloroquine.

While the COVID-19 epidemic occurred since December 2019, as of end April 2020, no treatment has been validated or invalidated by accurate clinical trials. Use of hydroxychloroquine has been popularised on mass media and put forward as a valid treatment option without strong evidence of efficacy. Hydroxychloroquine (HCQ) has its own side effects, some of which are very serious like acute haemolysis in glucose-6-phosphate dehydrogenase (G6PD) deficient patients. Side effects may be worse than the disease itself. Belgian national treatment guidelines recommend the use of HCQ in mild to severe COVID-19 disease. As opinions, politics, media and beliefs are governing COVID-19 therapy, performance of randomised controlled blinded clinical trials became difficult. Results of sound clinical trials are eagerly awaited. We report a case of acute haemolysis leading to admission in intensive care unit and renal failure in a patient with uncovered G6PD deficiency.

COVID-19 infection and treatment with hydroxychloroquine cause severe haemolysis crisis in a patient with glucose-6-phosphate dehydrogenase deficiency.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an inherited genetic disorder caused by red cell enzymatic defects and is associated with haemolytic crisis when patients are exposed to oxidative agents (fava beans, drugs, infections). Hydroxychloroquine is suspected to trigger haemolytic crisis in G6PD-deficient patients, and off-label administration of this drug to patients infected with the novel coronavirus (SARS-CoV-2) could cause concern. We report here the first case of severe haemolytic crisis in a patient with G6PD deficiency, initiated by severe COVID-19 infection and hydroxychloroquine use. With worldwide spread of COVID-19, especially in regions with a high prevalence of G6PD deficiency, our case should alert physicians to this possible correlation.