Glucosephosphate Dehydrogenase Deficiency

Publication Title: 
Free Radical Research

Previous studies have shown that glucose-6-phosphate dehydrogenase (G6PD)-deficient cells are under increased oxidative stress and undergo premature cellular senescence. The present study demonstrates that G6PD-deficient cells cultured under 3% oxygen concentration had an extended replicative lifespan, as compared with those cultured under atmospheric oxygen level. This was accompanied by a reduction in the number of senescence-associated beta-galactosidase (SA-beta-Gal) positive and morphologically senile cells at comparable population doubling levels (PDL).

Author(s): 
Ho, Hung-Yao
Cheng, Mei-Ling
Cheng, Pei-Fen
Chiu, Daniel Tsun-Yee
Publication Title: 
Cardiovascular & Hematological Disorders Drug Targets

We review here some recent data about Glucose-6-phosphate dehydrogenase (G6PD), the housekeeping X-linked gene encoding the first enzyme of the pentose phosphate pathway (PPP), a NADPH-producing dehydrogenase. This enzyme has been popular among clinicians, biochemists, geneticists and molecular biologists because it is the most common form of red blood cell enzymopathy. G6PD deficient erythrocytes do not generate NADPH in any other way than through the PPP and for this reason they are more susceptible than any other cells to oxidative damage.

Author(s): 
Manganelli, Genesia
Masullo, Ugo
Passarelli, Stefania
Filosa, Stefania
Publication Title: 
PloS One

BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common inherited human enzyme defect. This deficiency provides some protection from clinical malaria, but it can also cause haemolysis after administration of drugs with oxidant properties. METHODS: The safety of chlorproguanil-dapsone+artesunate (CD+A) and amodiaquine+sulphadoxine-pyrimethamine (AQ+SP) for the treatment of uncomplicated P. falciparum malaria was evaluated according to G6PD deficiency in a secondary analysis of an open-label, randomized clinical trial.

Author(s): 
Fanello, Caterina I.
Karema, Corine
Avellino, Pamela
Bancone, Germana
Uwimana, Aline
Lee, Sue J.
D'Alessandro, Umberto
Modiano, David
Publication Title: 
Antimicrobial Agents and Chemotherapy

The current interest in malaria elimination has led to a renewed interest in drugs that can be used for mass administration to minimize malaria transmission. Primaquine (PQ) is the only generally available drug with a strong activity against mature Plasmodium falciparum gametocytes, the parasite stage responsible for transmission. Despite concerns about PQ-induced hemolysis in glucose-6-phosphate dehydrogenase (G6PD)-deficient individuals, a single dose of PQ may be safe and efficacious in clearing gametocytes that persist after conventional treatment.

Author(s): 
Shekalaghe, Seif A.
ter Braak, Roel
Daou, Modibo
Kavishe, Reginald
van den Bijllaardt, Wouter
van den Bosch, Sven
Koenderink, Jan B.
Luty, Adrian J. F.
Whitty, Christopher J. M.
Drakeley, Chris
Sauerwein, Robert W.
Bousema, Teun
Publication Title: 
Malaria Journal

BACKGROUND: Artemisinin-based combination therapy (ACT) is currently the most effective medicine for the treatment of uncomplicated malaria. Artemisinin has previously been shown to increase the clearance of Plasmodium falciparum in malaria patients with haemoglobin E trait, but it did not increase parasite inhibition in an in vitro study using haemoglobin AS erythrocytes. The current study describes the efficacy of artemisinin derivatives on P.

Author(s): 
Kone, Abdoulaye K.
Sagara, Issaka
Thera, Mahamadou A.
Dicko, Alassane
Guindo, Aldiouma
Diakite, Seidina
Kurantsin-Mills, Joseph
Djimde, Abdoulaye
Walcourt, Asikiya
Doumbo, Ogabara
Publication Title: 
PLoS medicine

Antimalarial drugs will be essential tools at all stages of malaria elimination along the path towards eradication, including the early control or "attack" phase to drive down transmission and the later stages of maintaining interruption of transmission, preventing reintroduction of malaria, and eliminating the last residual foci of infection.

Author(s): 
malERA Consultative Group on Drugs
Publication Title: 
Malaria Journal

BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is common in populations living in malaria endemic areas. G6PD genotype and phenotype were determined for malaria patients enrolled in the chlorproguanil-dapsone-artesunate (CDA) phase III clinical trial programme. METHODS: Study participants, aged > 1 year, with microscopically confirmed uncomplicated Plasmodium falciparum malaria, and haemoglobin ? 70 g/L or haematocrit ? 25%, were recruited into two clinical trials conducted in six African countries (Burkina Faso, Ghana, Kenya, Nigeria, Tanzania, Mali).

Author(s): 
Carter, Nick
Pamba, Allan
Duparc, Stephan
Waitumbi, John N.
Publication Title: 
Antimicrobial Agents and Chemotherapy

Primaquine is currently the only drug available for radical cure of Plasmodium vivax and P. ovale liver infection stages, but limited safety data exist for children <10 years of age. Detailed daily assessments of side effects in glucose-6-phosphate dehydrogenase (G6PD)-normal children treated with 14 days of primaquine plus chloroquine (3 days; n = 252) or artesunate (7 days; n = 141) (0.5 mg/kg of body weight) showed that both treatments are well tolerated, do not lead to reductions in hemoglobin levels, and can thus safely be used in children 1 to 10 years of age.

Author(s): 
Betuela, Inoni
Bassat, Quique
Kiniboro, Benson
Robinson, Leanne J.
Rosanas-Urgell, Anna
Stanisic, Danielle
Siba, Peter M.
Alonso, Pedro L.
Mueller, Ivo
Publication Title: 
Malaria Journal

BACKGROUND: Malaria is a leading cause of mortality, particularly in sub-Saharan African children. Prompt and efficacious treatment is important as patients may progress within a few hours to severe and possibly fatal disease. Chlorproguanil-dapsone-artesunate (CDA) was a promising artemisinin-based combination therapy (ACT), but its development was prematurely stopped because of safety concerns secondary to its associated risk of haemolytic anaemia in glucose-6-phosphate dehydrogenase (G6PD)-deficient individuals.

Author(s): 
Van Malderen, Carine
Van Geertruyden, Jean-Pierre
Machevo, Sonia
González, Raquel
Bassat, Quique
Talisuna, Ambrose
Yeka, Adoke
Nabasumba, Carolyn
Piola, Patrice
Daniel, Atwine
Turyakira, Eleanor
Forret, Pascale
Van Overmeir, Chantal
van Loen, Harry
Robert, Annie
D' Alessandro, Umberto
Publication Title: 
PLoS medicine

BACKGROUND: Primaquine is a key drug for malaria elimination. In addition to being the only drug active against the dormant relapsing forms of Plasmodium vivax, primaquine is the sole effective treatment of infectious P. falciparum gametocytes, and may interrupt transmission and help contain the spread of artemisinin resistance. However, primaquine can trigger haemolysis in patients with a deficiency in glucose-6-phosphate dehydrogenase (G6PDd). Poor information is available about the distribution of individuals at risk of primaquine-induced haemolysis.

Author(s): 
Howes, Rosalind E.
Piel, Frédéric B.
Patil, Anand P.
Nyangiri, Oscar A.
Gething, Peter W.
Dewi, Mewahyu
Hogg, Mariana M.
Battle, Katherine E.
Padilla, Carmencita D.
Baird, J. Kevin
Hay, Simon I.

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