Prevalence of glucose-6-phosphate dehydrogenase deficiency and its association with Plasmodium falciparum infection among children in Iganga distric in Uganda

BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) is a metabolic enzyme involved in the pentose phosphate pathway, its especially important in red blood cell metabolism. Glucose-6-phosphate dehydrogenase deficiency is an X-linked recessive hereditary disease characterised by abnormally low levels of G6PD. About 400 million people worldwide have a deficiency of this enzyme. The remarkable geographic correlation of G6PD deficiency distribution with historical endemicity patterns of malaria has led to suggestions that the two could be linked. Some studies have concluded that G6PD deficiency confers resistance to malaria. OBJECTIVE: To determine the prevalence of G6PD deficiency, and determine its relationship with prevalence and incidence of P. falciparum infection among children in Uganda. METHODS: This was longitudinal study involving 245 children, 135 were actively followed up for 12 months. G6PD status was assessed for using PCR-RFLP method. A thick smear was done to determine presence of plasmodium trophozoites and parasite densities. RESULTS: A total of 245 children between 6 months and 9 years were recruited. Of these 46.5% were males. Overall prevalence for the X-linked G6PD A- mutation was; 79.59% wild type, 12.65% heterozygous and 7.76% homozygous or hemizygous. Among the males 14% were hemizygous. At baseline, 40.8% had asymptomatic P falciparum infection. There was no statistically significant difference in prevalence and incidence rates of malaria infection among the different G6PD genotypes with prevalence among heterozygous, homozygous, and wild type being 29%, 42.6% and 43% respectively (p = 0.11) and incidence among heterozygous and wild type being 0.56 and 0.52 episodes/year (p = 0.5). The heterozygous G6PD A- females had a lower parasite density compared to the wild type (2505 vs 941 parasites/μL; P = 0.024). CONCLUSIONS: This study showed that 20.41% of the population in this part of Uganda carry the G6PD A-mutation, within the range of 15-32% seen in other parts of Africa. P. falciparum infection incidence and prevalence rates are similar among the G6PD genotypes though, once infected, P. falciparum parasite densities are lowest among G6PD A- heterozygous females. This suggests differences in P. falciparum infection rates and severity of disease could be mediated by differences in parasite densities among the different G6PD genotypes

Genetic disorders and malaria in Indo-China region

High prevalence of malaria in Southeast Asia including Thailand is believed to be a major public health problem to the population in this area since time immemorial. Adaptation of the population in this area following the principle of natural selection coupled with genetic disorders can be expected. Some good examples for natural selection of malaria are the co-existence of high prevalence of thalassaemia as well as glucose-6-phosphate dehydrogenase deficiency. In this report, general aspects of some important genetic disorders and malaria in Indo-China area (Thailand, Laos, Cambodia, Myanmar, Vietnam, Yunnan and Manipur) are summarized and discussed

Inherited hemolytic disorders with high occurrence of b-thalassemia in Sindhi community of Jabalpur town in Madhya Pradesh, India

Hereditary hemolytic disorders such as hemoglobin disorders, β-thalassemia syndrome, G6PD deficiency, and ABO and Rhesus blood groups are the most common public health problems in India. Community genetic screening provides multifaceted information for finding prevalence, level of health education, preventive strategies such as genetic/marriage counseling to relieve the burden of vulnerable communities. However, such genetic screening studies are scanty in India. This study aims to find the prevalence of inherited hemolytic disorders in Sindhi community, identify the persons for genetic/marriage counseling and to suggest the relevant strategies for prevention and control to the affected families. A cross-sectional random study of 508 persons of Sindhi community belonging to all ages and both sexes was conducted for screening of hemoglobin disorders, G6PD deficiency and ABO and Rhesus (D) blood groups following the standard procedures and techniques from Jabalpur town in Central India. High frequency of β-thalassemia trait (20.5%), Hb D trait (2.2%) and hemoglobin D/β-thalassemia (0.2%), G6PD deficiency (0.8%), and a low prevalence of Rhesus negative (3.0%) blood group was observed in Sindhi community of Jabalpur town in Madhya Pradesh. A case of β-thalassemia major and Hb D-thalassemia were also encountered. Double heterozygosity of Hb D/β-thalassemia showed hypochromic and microcytic red cell morphology with mild anemia. Inherited hemolytic disorders are an important public health challenge in Sindhi community. Preventive genetics program needs to be vigorously taken up to ameliorate the sufferings of at risk communities in India

Nutritional status of young children with inherited blood disorders in western Kenya.

To determine the association between a range of inherited blood disorders and indicators of poor nutrition, we analyzed data from a population-based, cross-sectional survey of 882 children 6–35 months of age in western Kenya. Of children with valid measurements, 71.7% were anemic (hemoglobin < 11 g/dL), 19.1% had ferritin levels < 12 μg/L, and 30.9% had retinol binding protein (RBP) levels < 0.7 μmol/L. Unadjusted analyses showed that compared with normal children, homozygous α(+)-thalassemia individuals had a higher prevalence of anemia (82.3% versus 66.8%, P = 0.001), but a lower prevalence of low RBP (20.5% versus 31.4%, P = 0.024). In multivariable analysis, homozygous α(+)-thalassemia remained associated with anemia (adjusted odds ratio [aOR] = 1.8, P = 0.004) but not with low RBP (aOR = 0.6, P = 0.065). Among young Kenyan children, α(+)-thalassemia is associated with anemia, whereas G6PD deficiency, haptoglobin 2-2, and HbS are not; none of these blood disorders are associated with iron deficiency, vitamin A deficiency, or poor growth

Glucose-6-phosphate-dehydrogenase deficiency as a risk factor in proliferative disorder development

Glucose-6-phosphate dehydrogenase (G6PD) is an important site of metabolic control in the pentose phosphate pathway (PPP) which provides reducing power (NADPH) and pentose phosphates. The former is mainly involved in the detoxification of chemical reactive species; the latter in the regulation of cell proliferation. G6PD deficiency is the most common enzymopathy in the human population, characterized by decreased G6PD activity, mainly in red blood cells, but actually also in nucleated cells. This decreased activity is not due to enzyme synthesis impairment, but rather to reduced enzyme stability, which leads to a shortening of its half-life. Therefore, a major problem is to understand the underlying mechanisms linking G6PD deficiency to oxidative stress and cell proliferation. In order to address this issue, in the present study we utilized, as an experimental model, fibroblasts isolated from pterygium, an ocular proliferative lesion, from G6PD normal and deficient (PFs+ and PFs-, respectively) patients. Our choice was determined by the fact that pterygium is believed to be caused by chronic oxidative stress induced by UV exposure, and that pterygium fibroblasts resemble a tumorigenic phenotype. As controls we utilized fibroblasts isolated from conjunctiva from G6PD normal and deficient patients (NCFs+ and NCFs-, respectively) who had undergone cataract surgery. &#xd;&#xa;Growth rate analysis revealed that PFs grow faster than NCFs, but while NCFs- grow more slowly than NCFs+, PFs- and PFs+ grow at the same rate. This was associated with significantly lower G6PD activity in NCFs+ compared to NCFs-, while no significant differences in the G6PD activity of PFs+ and PFs- were noted. This result was supported by the finding that in PFs-, G6PD mRNA levels were significantly higher than in PFs+. Another interesting finding of this study was increased green autofluorescence in both NCFs- and PFs- compared to corresponding positive cells, indicative of pronounced oxidative stress in deficient cells. Finally, abnormal accumulation of neutral lipids, mainly cholesterol esters was observed both in PFs- and PFs+ compared to NCFs- and NCFs+. Though further studies are necessary for better understanding the exact mechanism which links G6PD to oxidative stress and cell proliferation, our data allow to speculate on the role of G6PD on tumorigenesis, and to consider G6PD-deficient subjects at major risk to develop common and dreaded proliferative disorders, such as atherosclerosis and cancer. &#xd;&#xa

Molecular characterization of glucose-6-phosphate dehydrogenase deficiency in Jeddah, Kingdom of Saudi Arabia

International audienceABSTRACT: BACKGROUND: The development of polymerase chain reaction (PCR)-based methods for the detection of known mutations has facilitated detecting specific red blood cell (RBC) enzyme deficiencies. We carried out a study on glucose-6-phosphate dehydrogenase (G6PD) deficient subjects in Jeddah to evaluate the molecular characteristics of this enzyme deficiency and the frequency of nucleotide1311 and IVS-XI-93 polymorphisms in the glucose-6-phosphate dehydrogenase gene. RESULTS: A total of 1584 unrelated Saudis (984 neonates and 600 adults) were screened for glucose-6-phosphate dehydrogenase deficiency. The prevalence of glucose-6-phosphate dehydrogenase deficiency was 6.9% (n=110). G6PD Mediterranean mutation was observed in 98 (89.1%) cases, G6PD Aures in 11 (10.0%) cases, and G6PD Chatham in 1 (0.9%) case. None of the samples showed G6PD A mutation. Samples from 29 deficient subjects (25 males and 4 females) were examined for polymorphism. The association of two polymorphisms of exon/intron 11 (c.1311T/IVS XI 93C) was observed in 14 (42.4%) of 33 chromosomes studied. This association was found in 9 (31.0%) carriers of G6PD Mediterranean and in 4 (13.8%) carriers of G6PD Aures. CONCLUSIONS: The majority of mutations were G6PD Mediterranean, followed by G6PD Aures and <1% G6PD Chatham. We conclude that 1311T is a frequent polymorphism in subjects with G6PD Mediterranean and Aures variants in Jeddah

Genetic Disease Burden, Nutrition and Determinants of Tribal Health Care in Chhattisgarh State of Central-East India: A Status Paper

Tribal health is an important aspect of development and progress of the people. This study pertaining to genetic disease burden, nutritional status and biomedical anthropological assessment with particular reference to determinants of tribal health care has been carried out among the four tribes, namely, Bhatra, Gond, Kondh and Paraja of Orissa residing adjacent to the bordering districts of Chhattisgarh The population genetic structure of a tribe is the outcome of socio-cultural practices, bio-psychological behavior, genetic constitution, and eco-environmental conditions. Tribal communities in India, in general and of Chhattisgarh state in particular, are highly vulnerable to various genetic diseases, nutritional deficiencies and unrealistic practices and lack of access to basic health facilities. A total of 815 blood samples comprising of 166 Bhatra, 219 Gond, 254 Kondh and 176 Paraja tribes were collected randomly under aseptic conditions. The frequency of sickle cell hemoglobinopathy (3.2-22.5%), β-thalassemia trait (0.5-8.5%), and G6PD enzyme deficiency (6-16%) is very high among the tribes of Chhattisgarh. However, the prevalence of Rhesus negative blood group is very low (0-0.6%). The frequency of hereditary hemolytic anemia is also high among the tribals of Chhattisgarh. Both communicable and non-communicable diseases harbor the tribal population. The nutritional deficiencies are rampant. Tribal people are engrossed with superstitions and have faith in traditional healers who practice magico-religious rites along with indigenous herbal treatment for the common ailments. Traditional folk medicine and health culture play a significant role in shaping tribal life. These health practices differ from one tribe to another. Unless locality specific, tribe specific and need-based health care system is evolved which should be appropriate, acceptable, accessible, and affordable, the true goal of health for all cannot be achieved in India

Glucose 6 phosphate dehydrogenase levels in babies delivered at the University of Ilorin teaching hospital.

Background: Glucose-6-phosphate dehydrogenase deficiency, an X-linked recessive disorder, is the most common enzymopathy producing disease in humans.It is known to cause severe neonatal hyperbilirubinaemia. Aims and Objectives: To determine G6PD levels in babies delivered at the University of Ilorin Teaching Hospital with a view to determining the prevalence of G6PDdeficiency. Methods: Samples of cord blood were collected at delivery, from 933 babies who met set criteria. Blood was assayed for G6PD levels using a quantitative in vitro test (RANDOX&copy;). Results: A total of 348 (37.3%) of the 933 tested subjects had G6PD deficiency with enzyme activity of &le; 2.8U/gHb. Glucose 6 Phosphate Dehydrogenase levels in female babies with normal enzyme levels were significantly higher than in male babies with normal enzyme levels (5.72 &plusmn; 2.45 U/gHb versus 4.99 &plusmn; 2.3 U/gHb, p = 0.002). Enzyme levels in babies with G6PD deficiency was comparable in both males and females (2.05 &plusmn; 0.60 u/gHb in females and 2.1 &plusmn; 0.66 U/gHb in males, p = 0.66). The prevalence of G6PD deficiency was comparable among males and females (p = 0.81 &Chi;&sup2;= 0.06, RR = 1.02 , CI = 0.9 0 &lt; R R &lt; 1.15 , OR=1.04). Conclusion: There is a high prevalence of G6PD deficiency in babies delivered at the University of Ilorin Teaching Hospital, and the enzyme deficiency appears to occur equally among the sexes.Key words: Glucose-6-phosphate, neonates, cord bloo

Determining the frequency of glucose-6-phosphate dehydrogenase deficiency in newborn infants in Shahrekord

زمینه و هدف: گلوکز -6- فسفات دهیدروژناز (G6PD) اولین آنزیم در مسیر متابولیسم پنتوز فسفات می باشد. این مسیر در از بین بردن متابولیت های اکسیدان در بدن نقش موثری را ایفا می کند. کمبود این آنزیم باعث کاهش احیاء انرژی گلبول های قرمز و همولیز می‌گردد. در این مطالعه استفاده از روش غربالگری جهت تعیین میزان فراوانی کمبود آنزیم G6PD در نوزادان تازه متولد شده مورد بررسی قرار گرفت. روش بررسی: در این مطالعه توصیفی- مقطعی از بند ناف 1240 نوزاد تازه به دنیا آمده نمونه سرم تهیه شد و با استفاده از روش فلورسانس لکه ای میزان فعالیت آنزیم G6PD تعیین گردید. اطلاعات دموگرافیک شامل محل زندگی، جنس، سابقه کمبود G6PDدر خانواده و بستری به علت زردی تکمیل شد. داده ها با استفاده از نرم افزار آماری SPSS و آزمون آماری کای دو مورد تجزیه و تحلیل قرار گرفت. یافته ها: از کل 1240 نمونه مورد بررسی 29 نفر (3/2) دچار کمبود G6PDبودند، از بین افراد مبتلا، 3 نفر (3/10) از آنها کمبود شدید آنزیم G6PD و 26 نفر (7/89) کمبود خفیف تا متوسط داشتند. بین متغیرهای مورد بررسی و کمبود آنزیم، فقط موارد بستری به علت زردی ارتباط معنی داری با کمبود آنزیم داشت (001/0>P). نتیجه گیری: با توجه به درصد بالای بستری شدن نوزادان مبتلا به کمبودG6PD و خطراتی که این بیماری همولیتیک می تواند در آینده برای بیماران ایجاد کند و نظر به ارزان بودن تست فلورسنت لکه ای، می توان از این تست جهت غربالگری نوزادان تازه متولد شده استفاده کرد

Prospective evaluation of BDProbeTec strand displacement amplification (SDA) system for diagnosis of tuberculosis in non-respiratory and respiratory samples.

Nucleic acid amplification techniques (NAATs) have been demonstrated to make significant improvements in the diagnosis of tuberculosis (TB), particularly in the time to diagnosis and the diagnosis of smear-negative TB. The BD ProbeTec strand displacement amplification (SDA) system for the diagnosis of pulmonary and non-pulmonary tuberculosis was evaluated. A total of 689 samples were analysed from patients with clinically suspected TB. Compared with culture, the sensitivity and specificity for pulmonary samples were 98 and 89 %, and against final clinical diagnosis 93 and 92 %, respectively. This assay has undergone limited evaluation for non-respiratory samples and so 331 non-respiratory samples were tested, identifying those specimens that were likely to yield a useful result. These were CSF (n = 104), fine needle aspirates (n = 64) and pus (n = 41). Pleural fluid (n = 47) was identified as a poor specimen. A concern in using the SDA assay was that low-positive samples were difficult to interpret; 7.8 % of specimens fell into this category. Indeed, 64 % of the discrepant results, when compared to final clinical diagnosis, could be assigned as low-positive samples. Specimen type did not predict likelihood of a sample being in the low-positive zone. Although the manufacturers do not describe the concept of a low-positive zone, we have found that it aids clinical diagnosis