G6PD-deficient Patients Research Articles

<p>Clinical Characteristics of <em>Acalypha indica</em> Poisoning</p>

BackgroundAcalypha indica is a tropical plant used as a herbal medicine in various parts of the world, including Thailand. In glucose-6-phosphate dehydrogenase (G6PD)-deficient patients, acute hemolysis has been reported following the ingestion of this plant. Methemoglobinemia was reported in the present study.Patients and MethodsDescriptive data of patients who suffered from Acalypha indica toxicity reported from different hospitals to the Ramathibodi Poison Center were retrieved from 2011 to 2019.ResultsEight patients were included, mostly male with a median age of 61.5 years. The plant was ground for fresh juice or boiled before consuming as herbal medicine. All patients presented with dark urine. Most had jaundice and fever, and all reported hemolysis. Seven out of eight patients were diagnosed as methemoglobinemia. Methemoglobin level was confirmed in five patients with the highest level of 23.9%. Early symptoms occurred within 24 hours of the last ingested dose.DiscussionIn previous case reports of Acalypha indica ingestion, acute hemolysis was mostly observed in G6PD-deficient patients, consistent with the current findings. However, our patients also demonstrated methemoglobinemia, with some constituents in this plant (quinine, 2-methyl anthraquinone and tectoquinone) implicated as the cause in previous studies. Further studies are crucial to validate these findings.ConclusionWe report a case series in which acute hemolysis and methemoglobinemia after Acalypha indica ingestion were observed. This study presents methemoglobinemia as the other toxicity caused by this plant.

Hydroxychloroquine (HCQ) use in G6PD deficient COVID-19 patients and the risk of Acute Hemeolytic Anaemia (AHA).

Hydroxychloroquine (HCQ) use in G6PD deficient COVID-19 patients and the risk of Acute Hemeolytic Anaemia (AHA).

Molecular Characterization of Glucose-6-Phosphate Dehydrogenase: Do Single Nucleotide Polymorphisms Affect Hematological Parameters in HIV-Positive Patients?

This descriptive, cross-sectional study aimed at evaluating the prevalence of G6PD deficiency and the 376A ⟶ G, 202G ⟶ A single nucleotide polymorphisms (SNPs) among HIV patients attending care at a teaching hospital in Ghana and determine how the SNPs affect haematological profile in HIV. A total of 200 HIV-positive Ghanaians were recruited. Venous blood samples were obtained and complete blood count, and G6PD screening and genotyping for the 376A ⟶ G, 202G ⟶ A SNPs were performed. Out of the 200 participants, 13.0% (26/200) were G6PD-deficient based on the methemoglobin reductase technique, with 1.5% (3/200) and 11.5% (23/200) presenting with partial and full enzyme defect, respectively. Among the 13.0% participants with G6PD deficiency, 19.2% (5/26), 30.8% (8/26), and 19.2% (5/26) presented with 376A ⟶ G only (enzyme activity (EA): 1.19 U/g Hb), 202G ⟶A only (EA: 1.41 U/g Hb), and G202/A376 SNPs (EA: 1.14 U/g Hb), respectively. Having the 376A ⟶ G mutation was associated not only with lower red blood cell (RBC) count (3.38 × 106/µL (3.16–3.46) vs 3.95 × 106/µL (3.53–4.41), p = 0.010) but also with higher mean cell volume (MCV) (102.90 (99.40–113.0) vs 91.10 fL (84.65–98.98), p = 0.041) and mean cell haemoglobin (MCH) (33.70 pg (32.70–38.50) vs 30.75 pg (28.50–33.35), p = 0.038), whereas possessing the 202G ⟶ A mutation was associated with higher MCV only (98.90 fL (90.95–102.35) vs 91.10 fL (84.65–98.98), p = 0.041) compared to G6PD nondeficient participants. The prevalence of G6PD deficiency among HIV patients in Kumasi, Ghana, is 13.0% prevalence, comprising 1.5% and 11.5% partial and full enzyme defect, respectively, based on the methemoglobin reductase technique among HIV patients in Ghana. Among G6PD-deficient HIV patients, the prevalence of G202/A376 SNPs is 19.2%. The 376A ⟶ G mutation is associated not only with lower RBC count but also with higher MCV and MCH, whereas the 202G ⟶ A mutation is associated with higher MCV compared to the normal G6PD population.

Optimizing G6PD testing for Plasmodium vivax case management: why sex, counseling, and community engagement matter.

Safe access to the most effective treatment options for Plasmodium vivaxmalaria are limited by the absence of accurate point-of-care testingto detect glucose-6-phosphate dehydrogenase (G6PD) deficiency, the most common human genetic disorder. G6PD-deficient patients are at risk of life-threatening hemolysis when exposed to 8-aminoquinolines, the only class of drugs efficacious against P. vivaxhypnozoites. Until recently, only qualitative tests were available in most settings. These accurately identify patients with severe G6PD deficiency (mostly male) but not patients with intermediate G6PD deficiency (always female).This has led to and reinforced a gap in awareness in clinical practice of the risks and implications of G6PD deficiency in females-who, unlike males, can have a heterozygous genotype for G6PD.Increasing recognition of the need for radical cure of P. vivax, first for patients' health and then for malaria elimination, is driving the development of new point-of-care tests for G6PD deficiency and their accessibility to populations in low-resource settings. The availability of simple, affordable, and accurate point-of-care diagnostics for the precise classification of the three G6PD phenotypes can reduce sex-linked disparities by ensuring safe and effective malaria treatment, providing opportunities to develop supportive counseling to enhance understanding of genetic test results, and improving the detection of all G6PD deficiency phenotypes in newborns and their family members.

The modified G6PD deficiency screening test

Glucose-6-phosphate dehydrogenase (G6PD) deficiency, which involves the mutation of the G6PD gene on the X chromosome, is the most common enzyme defect in humans. G6PD produces nicotinamide adenine dinucleotide phosphate (NADPH) for red blood cell protection from oxidative stress. Oxidative stress-induced red blood cell hemolysis in G6PD-deficient patients leads to anemia, jaundice, acute renal failure, and kernicterus in newborns. Currently, the fluorescent spot test (FST) is widely used for G6PD deficiency screening. This test detects NADPH production under UV light. This study purposed to modify the G6PD deficiency screening test based on NADPH production and the ability to detect the results of the color change in the color of the reaction. Blood samples of 60 subjects were collected and screened for G6PD deficiency using FST method. All samples were tested with the modified G6PD screening test and the quantitative assay kit. The results from the modified test showed the color red for normal cases, whereas the color brown indicated G6PD deficiency cases. The cutoff value of G6PD activity detected by the quantitative method was less than 2.9 U/gHb for G6PD deficiency. The precision of this study was 100 %. The results of sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) of the modified test were 100 %, 96.7 %, 100 %, and 96.7 %, respectively. The modified G6PD screening test can be used for the screening of G6PD deficiency in newborns, for support through providing more information, and for self-protection from oxidative stress.

Ex Vivo Study of Laban's Role in Decreasing Hemolysis Crisis in G6PD-Deficient Patients.

In spite of the vast nutritional and environmental benefits provided by fava bean (Vicia faba), the ingestion of vicine/convicine provokes an acute hemolytic anemia called favism in individuals with a glucose-6-phosphate dehydrogenase (G6PD) deficiency. The elimination of these glycosides is a goal that could be accomplished using different processing methods including bacteriological treatment. Laban as a good source of lactic acid bacteria was tested in an ex vivo assay on human blood samples in order to determine its capacity in decreasing the hemolysis crisis induced by the ingestion of fava beans. Results indicate a significant decrease in human blood cell hemolysis after the treatment of fava beans by Laban. This decrease in hemolysis was also correlated with the G6PD deficiency categorization. The highest hemolysis level (mean: 23.11 ± 0.76%) was observed in samples with G6PD activity between 10 and 30%, while the lowest hemolysis level (mean: 5.75 ± 0.64%) was observed in samples with G6PD activity more than 60%. This decrease was correlated with a high antioxidant capacity of Laban (51.61 ± 1.13% expressed by the percentage inhibition of DPPH radical). The counts of isolates from MRS and M17 culture plates were 6.75 ± 0.095 and 7.91 ± 0.061 log cfu ml–1, respectively. In conclusion, the synergy between the antioxidant properties of Laban and the possible decrease of vicine and convicine concentrations by lactobacillus found in the fermented dairy products could explain the ability of Laban to reduce the hemolysis crisis ex vivo.

Recent trends of glucose-6-phosphate dehydrogenase deficiency among saudi population in Riyadh city

G6PD deficiency is associated with erythrocyte deficiency in the X-chromosome enzyme. It causes a hematologic syndrome called hemolytic anemia that connects G6PD deficiency with X-linked condition. In the Middle East, including Saudi Arabia, G6PD deficiency is the most dominant genetic blood disorders. It results in higher rates of mortality and morbidity due to its incurable long-lasting nature and prevalence of physical and psychological incapacities. In this study, an attempt was made to evaluate the prevalence of G6PD deficiency among the Saudi population in Riyadh city. A cross-sectional retrospective study was conducted at King Saud University Medical City in Riyadh, Saudi Arabia. The population of the study comprised randomly chosen males and females who visited the hospital from January 2017 to January 2018. Statistical analyses were performed using SPSS, and descriptive analysis was used to find the frequency of G6PD-deficient patients. Out of the 209 patients, 62.2% were males (n=130) and 37.8% were females (n=79). Twenty males and 6 females were found to have G6PD deficiency, with the male to female ratio being 1:3. Out of the total 130 male participants, 20 patients were found to be enzyme deficient and 6 patients of 79 female patients were found to be G6PD deficient. There were 38.4% (n=10) patients with G6PD level <4 units/gram hemoglobin, 26.9% (n=7) patients had G6PD levels of 4.1–7.0 units/gram hemoglobin, and 34.6% (n=9) patients had >7 units/gram hemoglobin. Among the G6PD patients, 23.07% patients were severely anemic, and 5 (19.2%) patients were reported to have high bilirubin. The present study revealed the G6PD prevalence to be 12.4% among the Saudi population; this value is significantly higher than that found in France, Spain, India, and Singapore. In the Saudi population, males are more vulnerable to G6PD-deficient than females. Hence, attention should be paid to G6PD-deficient patients while prescribing antimalarial medication. Such patients may be advised to avoid certain foods to minimize the risk of having hemolytic episodes.

Molecular Characterization of G6PD Deficiency: Report of Three Novel G6PD Variants.

G6PD deficiency is a monogenic, X-linked genetic defect with a worldwide prevalence of around 400 million people and an overall prevalence of 8.5% in India. Hemolytic anemia is encountered in only a small proportion of patients with G6PD variants and is usually triggered by some exogenous agent. Although G6PD deficiency was reported in India more than 50years ago, there are very few studies on molecular characterization and phenotypic correlation in G6PD deficient patients. We aimed to study the epidemiology and correlate the phenotypic expression with molecular genotypes in symptomatic G6PD deficient patients. All symptomatic hemolytic anaemia patients with a possible etiology of G6PD deficiency based on the clinical, hematological and biochemical parameters and reduced G6PD enzyme levels were included in this study. Molecular analysis of the G6PD gene was done by direct Sanger sequencing. From a total of 38 patients with hemolytic anemia suspected for G6PD deficiency, 24 patients had reduced G6PD enzyme levels and were included for the molecular analysis and mutations in the G6PD gene were identified in 21 of them (83.3%). The different mutations identified in our study include 6 patients with c.131C > G (G6PD Orissa), 3 patients with c.563C > T (G6PD Mediterranean), two patients with c.825G > T (G6PD Bangkok), one patient each with c.208T > C (G6PD Namouru), c.487G > A (G6PD Mahidol), c.949G > A (G6PD Kerala-Kalyan), c.100 G > A (G6PD Chatham), c.1178C > G (G6PD Nashville), c.1361 G > A (G6PD Andalus) and 4 patients with novel mutations (2 patients with c.1186C > T and 1 patient each with c.1288-2A > T and c.1372C > T. No disease causing genetic variants were identified in the other three cases. Co-inheritance of other red cell and hemoglobin disorders can modify the clinical phenotype of G6PD patients and the diagnostic accuracy can be improved by molecular characterization of the variant.

Tafenoquine for the prophylaxis, treatment and elimination of malaria: eagerness must meet prudence.

Malaria puts more than 3 billion people at risk of infection and causes high morbidity and mortality. Plasmodium vivax forms hypnozoites, which may initiate recurrences, even in the absence of reinfection or superinfection. Until recently, the only drug available for eliminating hypnozoites was primaquine (PQ), which, given its short half-life, requires a relatively long course of treatment. Tafenoquine (TQ) is a PQ analog with a longer half-life. This enables radical cure of malaria with a single dose and overcomes adherence issues associated with PQ, thereby increasing effectiveness in real-life settings. Clinical studies have provided sound evidence for TQ's safety and efficacy against malaria, which recently led to its approval by the US FDA. Here, we review aspects of TQ, including how to avoid hemolytic anemia in G6PD deficient patients. We believe that TQ promises to be a major advance toward malaria elimination.

Clinical presentation and Predictors of mortality in severe malaria in pediatric population: A prospective observational study

Background: Malaria remains a significant public health in India and a major cause of under 5 mortality. Clinical manifestations of malaria in children may differ significantly from adults and there is wide variation in manifestation depending on endemicity. We conducted this study to find the clinical presentation and features which would predict mortality in children with severe malaria. Methods: a prospective observational study was conducted at Pediatric units of SCB Medical College, Cuttack. Children below 14 years of age with confirmed diagnosis of malaria and satisfying the WHO criteria for severe malaria were included in the study. Baseline demographic data collected and clinical features during the course of illness were documented. Logistic regression analysis was used to find the predicting factors for mortality. Result: out of 557 cases with malaria over a period of 20 months, 130 patients (23.3%) satisfied the WHO criteria for severe malaria. Case fatality rate was 8.5%. Apart from fever, anemia and prostration were most commonly associated complications. Presence of respiratory distress, CNS involvement, shock and renal failure were found to be the major predictor of death. Risk of mortality increased significantly with the presence of multiple organ dysfunction. About 12.3% of the patients were G6PD deficient. A higher incidence of hemoglobinuria and a lower incidence of cerebral malaria was observed in G6PD deficient patients. Conclusion: Complications associated with severe malaria in pediatric populations in India differ from African countries. Multiple organ dysfunction is not uncommon in the pediatric population and it significantly increases the chances of adverse outcome.

Glucose-6-phosphate dehydrogenase deficiency reduces susceptibility to cancer of endodermal origin

Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common inherited enzyme defect worldwide. There is a growing scientific evidence for a protective role of G6PD deficiency against carcinogenesis. In this retrospective analysis, we tested the hypothesis that G6PD deficiency may reduce the risk of developing cancer in a tissue-specific manner.Material and methods: The study was conducted using data from 11,708 subjects undergoing gastrointestinal endoscopic procedures between 2002 and 2018 and tested for G6PD status in a teaching hospital of Northern Sardinia, Italy.Results: A 40% reduction of risk for cancer of endodermal origin was observed among G6PD-deficient patients compared with subjects with normal enzyme activity (relative risk (RR) 0.61, 95% confidence interval (CI) 0.47–0.80) in both genders, confirmed by multivariable generalized linear regression after adjusting for age, sex, smoking habits, body mass index, diabetes and socio-economic status. The ‘protective’ effect of G6PD deficiency was larger for gastric cancer (RR 0.41, 95% CI 0.18–0.99), hepatocellular carcinoma (RR 0.48, 95% CI 0.26–0.92) and colorectal cancer (RR 0.72, 95% CI 0.53–0.98), while a non-significant risk was observed for breast, prostate, lung, hematopoietic and metastases (primary site unknown).Conclusions: Our results suggest a reduced susceptibility to develop cancers, mostly of endodermal origin (stomach, colon and liver), but not of ectodermal/mesodermal origin, in carriers of G6PD deficiency. The effects of G6PD deficiency on carcinogenesis need further studies to better understand how cancer cells originating from different germ layers use pentose phosphate pathway to proliferate.

105P - Safe chemotherapy for treating early breast cancer in G6PD-deficient patients

105P - Safe chemotherapy for treating early breast cancer in G6PD-deficient patients

Prevalence and Genetic Characterization of Glucose-6-Phosphate Dehydrogenase Deficiency in Anemic Subjects from Uttar Pradesh, India.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is caused by one or more mutations in the G6PD gene on chromosome X. It affects approximately 400 million people worldwide. The purpose of this study was to detect the prevalence of G6PD deficiency and G6PD gene mutations in the hospital-based settings in patients referred for suspected G6PD deficiency. A qualitative fluorescent spot test and dichlorophenol-indolphenol (DCIP) test were performed. G6PD-deficient, positive samples were further processed for mutation analysis by Sanger sequencing. Out of 1,069 cases, 95 (8.8%) were detected as G6PD deficient (by DCIP test) and were sent for molecular analysis. The G6PD Mediterranean mutation (563C > T) is the most common variant among G6PD-deficient individuals followed by the Coimbra (592C→T) and Orissa (131C→G) variants. We concluded that all symptomatic patients (anemic or jaundiced) should be investigated for G6PD deficiency. Our findings will inform our population screening approach and help provide better management for G6PD-deficient patients.

A vegetable-induced hemolytic crisis in a G6PD deficient person: a case report

BackgroundHemolysis can occur in people with G6PD deficiency under oxidative stress. Acalypha indica is a tropical plant used as a medicinal plant as well as a vegetable. There are a few reported cases of Acalypha indica ingestion induced hemolysis in G6PD deficient people. All except one of them are from Sri Lanka. The information available at present (2017) about G6PD deficiency prevalence and variants of the G6PD gene among Sri Lankans is very sparse. There are no past reports on hemolytic crisis in a G6PD deficient person presenting mimicking leptospirosis.Case presentationA middle-aged Sri Lankan man presented on the third day of illness complaining of fever, head ache, arthralgia, myalgia, abdominal pain, vomiting, passing dark urine and reduced of urine volume. He gave a history of possible exposure to leptospirosis. He was pale, icteric and his liver was palpable 1 cm below costal margin and there were no other remarkable findings upon physical examination. He had neutrophilic leucocytosis. Leptospirosis was diagnosed. During the second assessment we noticed he was very pale and his urine sample pointed towards hemoglobinuria. Further questioning revealed he had consumed leaves of Acalypha indica as a vegetable. Acute hemolysis in a G6PD deficient patient following Acalypha indica ingestion was diagnosed. Blood transfusions were given to correct his anemia. Later, Brewer’s test and quantitative assay of G6PD levels confirmed the diagnosis of G6PD deficiency.ConclusionsA hemolytic crisis following oxidative stresses in G6PD deficient patients can present mimicking leptospirosis. Further investigations may reveal why the great majority of cases of acute hemolysis in G6PD deficient person following Acalypha indica ingestion are from Sri Lanka.

Machine learning prioritizes synthesis of primaquine ureidoamides with high antimalarial activity and attenuated cytotoxicity

Primaquine (PQ) is a commonly used drug that can prevent the transmission of Plasmodium falciparum malaria, however toxicity limits its use. We prepared five groups of PQ derivatives: amides 1a-k, ureas 2a-k, semicarbazides 3a,b, acylsemicarbazides 4a-k and bis-ureas 5a-v, and evaluated them for antimalarial activity in vitro against the erythrocytic stage of P. falciparum NF54. Particular substituents, such as trityl (in 2j and 5r) and methoxybenzhydryl (in 3b and 5v) were associated with a favorable cytotoxicity-to-activity ratio. To systematically link structural features of PQ derivatives to antiplasmodial activity, we performed a quantitative structure-activity relationship (QSAR) study using the Support Vector Machines machine learning method. This yielded a highly accurate statistical model (R2 = 0.776 in cross-validation), which was used to prioritize novel candidate compounds. Seven novel PQ-ureidoamides 10a-g were synthesized and evaluated for activity, highlighting the benzhydryl ureidoamides 10e and 10f derived from p-chlorophenylglycine. Further experiments on human cell lines revealed that 10e and 10f are an order of magnitude less toxic than PQ in vitro while having antimalarial activity indistinguishable from PQ. The toxicity profile of novel compounds 10 toward human cells was particularly favorable when the glucose-6-phosphate dehydrogenase (G6PD) was inhibited, while toxicity of PQ was exacerbated by G6PD inhibition. Our work therefore highlights promising lead compounds for the development of effective antimalarial drugs that may also be safer for G6PD-deficient patients. In addition, we provide computational inferences of antimalarial activity and cytotoxicity for thousands of PQ-like molecular structures.

Glucose-6-Phosphate Dehydrogenase Deficiency Genetic Variants in Malaria Patients in Southwestern Ethiopia.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked erythrocyte enzyme disorder with relevance to malaria treatment policy. Treatment with the antimalarial primaquine can result in hemolytic anemia in G6PD-deficient patients. With increased interest in primaquine use, it is important to identify G6PD variants in Ethiopia to inform malaria treatment policy. In the present study, mutations in the G6PD gene are identified in a sample of patients with malaria in Jimma town in southwest Ethiopia. Plasmodium species of infection were confirmed using polymerase chain reaction (PCR) and gel electrophoresis. PCR and Sanger sequencing were performed to observe a portion of the G6PD gene where the common G6PD mutations (A376G, G202A, and C563T) are found. Molecular analysis revealed that most of the samples were single Plasmodium vivax infections (83.7%). For G6PD genotyping, A376G was detected in 23.26% of individuals, whereas G202A and C563T were absent. Three other uncommon mutations were identified: rs782669677 (535G→A), rs370658483, (485 + 37 G→T), and a new mutation at chrX:154535443(C→T). Bioinformatic analysis of these mutations' potential functional impact suggests minimal effect on protein function. The discovery of both common and uncommon G6PD mutations contributes to the discussion on G6PD deficiency and appropriate primaquine treatment in Ethiopia.

Tafenoquine for travelers' malaria: evidence, rationale and recommendations.

BackgroundEndemic malaria occurring across much of the globe threatens millions of exposed travelers. While unknown numbers of them suffer acute attacks while traveling, each year thousands return from travel and become stricken in the weeks and months following exposure. This represents perhaps the most serious, prevalent and complex problem faced by providers of travel medicine services. Since before World War II, travel medicine practice has relied on synthetic suppressive blood schizontocidal drugs to prevent malaria during exposure, and has applied primaquine for presumptive anti-relapse therapy (post-travel or post-diagnosis of Plasmodium vivax) since 1952. In 2018, the US Food and Drug Administration approved the uses of a new hepatic schizontocidal and hypnozoitocidal 8-aminoquinoline called tafenoquine for the respective prevention of all malarias and for the treatment of those that relapse (P. vivax and Plasmodium ovale).MethodsThe evidence and rationale for tafenoquine for the prevention and treatment of malaria was gathered by means of a standard search of the medical literature along with the package inserts for the tafenoquine products Arakoda™ and Krintafel™ for the prevention of all malarias and the treatment of relapsing malarias, respectively.ResultsThe development of tafenoquine—an endeavor of 40 years—at last brings two powerful advantages to travel medicine practice against the malaria threat: (i) a weekly regimen of causal prophylaxis; and (ii) a single-dose radical cure for patients infected by vivax or ovale malarias.ConclusionsAlthough broad clinical experience remains to be gathered, tafenoquine appears to promise more practical and effective prevention and treatment of malaria. Tafenoquine thus applied includes important biological and clinical complexities explained in this review, with particular regard to the problem of hemolytic toxicity in G6PD-deficient patients.

Safety and Efficacy of Adding a Single Low Dose of Primaquine to the Treatment of Adult Patients With Plasmodium falciparum Malaria in Senegal, to Reduce Gametocyte Carriage: A Randomized Controlled Trial.

More information is needed about the safety of low-dose primaquine in populations where G6PD deficiency is common. Adults with Plasmodium falciparum malaria were randomized to receive 1 of 3 artemisinin combination therapies (ACTs) with or without primaquine (0.25 mg/kg). Glucose-6-phosphate dehydrogenase (G6PD) status was determined using a rapid test. Patients were followed for 28 days to record hemoglobin concentration, adverse events, and gametocyte carriage. The primary end point was the change in Hb at day 7. In sum, 274 patients were randomized, 139 received an ACT alone, and 135 received an ACT + primaquine. The mean reduction in Hb at day 7 was similar in each group, a difference in the ACT + PQ versus the ACT alone group of -0.04 g/dL (95% confidence interval [CI] -0.23, 0.31), but the effect of primaquine differed according to G6PD status. In G6PD-deficient patients the drop in Hb was 0.63 g/dL (95% CI 0.03, 1.24) greater in those who received primaquine than in those who received an ACT alone. In G6PD-normal patients, the reduction in Hb was 0.22 g/dL (95% CI -0.08, 0.52) less in those who received primaquine (interaction P = .01). One G6PD normal patient who received primaquine developed moderately severe anaemia (Hb < 8 g/dL). Dark urine was more frequent in patients who received primaquine. Primaquine was associated with a 73% (95% CI 24-90) reduction in gametocyte carriage (P = .013). Primaquine substantially reduced gametocyte carriage. However, the fall in Hb concentration at day 7 was greater in G6PD-deficient patients who received primaquine than in those who did not and one patient who received primaquine developed moderately severe anemia. PACTR201411000937373 (www.pactr.org).

Role of primaquine in malaria control and elimination in French-speaking Africa

Primaquine, an 8-aminoquinoline, is a relatively unknown and underutilized drug in French-speaking African countries. It acts against the liver stage parasites of all human malaria species, asexual blood stages of Plasmodium vivax and, to a lesser degree, Plasmodium falciparum; P. falciparum mature gametocytes, and P. vivax and Plasmodium ovale hypnozoites. Gastrointestinal disturbances are its most common side effects. The clinical utility of primaquine is limited due to its hematological side effects in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency and other contraindications (pregnant woman, breastfeeding woman, infants less than 6 months old). In the light of the recent recommendations of the World Health Organization (WHO), we propose to examine how primaquine can be used in French-speaking Africa to improve malaria control and move towards malaria elimination. Two indications supported by the WHO are of relevance in Africa. First, artemisinin-based combination therapies and primaquine given as a single low dose (0.25 mg base/kg) are effective to kill asexual and sexual parasites of P. falciparum, are well-tolerated, and have very little risk even in mild to moderate G6PD-deficient patients. This strategy may be helpful to contain transmission in an area in Africa where P. falciparum malaria incidence has decreased considerably. There is an ethical concern in administering primaquine as a gametocytocide as it does not confer any direct benefit to the treated patient. However, the single low-dose primaquine is most likely associated with very low risk for adverse hematological effects, and WHO recommends its use even without prior G6PD testing. In our opinion, clinical studies including G6PD test should be conducted to assess the safety of low-dose primaquine in African patients. Second, primaquine is effective and necessary for radical treatment of P. vivax and P. ovale, but the standard 14-day treatment (0.25-0.5 mg base/kg/day) is not recommended in patients with G6PD deficiency. Prior G6PD testing is required before prescribing primaquine for radical treatment. The use of primaquine for radical treatment in patients without contraindications does not raise any major ethical problem since the probability of relapse in patients who do not receive anti-hypnozoite treatment can be relatively high and each relapse can cause or aggravate anemia, especially in children. In our opinion, patients with mild or moderate G6PD deficiency should not be treated with primaquine at present. Further clinical studies are necessary to define the role of this drug for radical treatment in G6PD-deficient African patients. Without primaquine, the eventual elimination of P. vivax and P. ovale malaria appears to be very difficult. Updated epidemiological data on G6PD, Duffy antigen, and the current distribution of and burden due to P. vivax and P. ovale are required for a rational use of primaquine in the African continent. Moreover, clinical studies on primaquine are required in Africa.

Influence of glucose-6 phosphate dehydrogenase (G6-PD) deficiency upon clinico-haematological and biochemical expression of patients with sickle cell disease

Background: According to world health organization, G6PD deficiency constitute 7.5% of world population as carriers whereas 2.9% as deficient. It has been reported from India that the prevalence varies from 0-27% in different caste, ethnic and linguistic groups. Various studies have revealed strong interaction between G6PD deficiency and sickle cell genes on one hand and environment on the other, one may therefore expect changes in their frequencies over a period of time in the population. We studied the influence of G6PD deficiency upon the clinico-haematological and biochemical expression of sickle cell disease.Methods: The study was carried out prospectively from September 2010 to August 2011 in the department of Pathology at our institute. The material for the present study consisted of 100 cases including 76 patients with Sickle cell disease and 24 of control group. On all the samples after screening and confirmatory tests, hematological and biochemical tests were performed and discussed along with their clinical profiles.Results: A total of 100 patients were studied, 76 were of sickle cell disease and remaining 24 patients were of control group. Majority of sickle cell trait (AS) patients (55.6%) and control patients (54%) had mild anaemia while most of the sickle cell anemia (SS) patients (44.4%) had moderate anaemia. The 2 (100%) AS and 1 (100%) control G6PD deficient patients had moderate anemia while the 2 (100%) SS patients with G6PD deficiency had severe anemia. All the sickle cell disease and control patients with G6PD deficient had elevated serum bilirubin and in all of them only unconjugated bilirubin was raised. None of the SS patients were asymptomatic. All the G6PD deficient patients had pallor and icterus. Vaso-occlusive crisis, acute chest syndrome and infectious episode were present in one (50%) each of AS and SS patients with G6PD deficiency.Conclusions: G6PD deficiency neither exacerbated nor mitigated the frequency of painful crisis, incidence of infection or anemic episodes in patients with sickle cell disease. Hematologically no significant differences were observed in sickle cell disease patients (AS and SS) with G6PD deficiency as compared to sickle cell disease patients without G6PD deficiency and the control.