Seven different glucose-6-phosphate dehydrogenase variants including a new variant distributed in Lam Dong Province in southern Vietnam.

We conducted a survey for glucose-6-phosphate dehydrogenase (G6PD) deficiency using blood samples from male outpatients of a local hospital in southern Vietnam. Most of the samples were from the Kinh (88.9%), the largest ethnic group in Vietnam, with a small number (11.1%) coming from the K'Ho, Chauma, Nung, and Tay minorities. We detected 25 G6PD-deficient cases among 1,104 samples (2.3%), and read the open reading frame of G6PD. A novel mutation (352T>C) predicting an aminoacid change of 118Tyr>His was found in a 1-year-old Kinh boy. His G6PD activity was estimated to be less than 10% residual activity, although he did not show chronic hemolytic anemia. Thus, we categorized this variant as Class II and named it G6PD Bao Loc. In the Kinh population, G6PD Viangchan (871G>A, 1311C>T, intron 11 nt93T>C), one of the most common variants in continental Southeast Asian populations, was the highest (6/19), followed by variants originating from the Chinese such as G6PD Canton (1376G>T) (5/19), G6PD Kaiping (1388G>A) (3/19), G6PD Gaohe (95A>G) (1/19), and G6PD Quing Yuan (392G>T) (1/19). In addition, G6PD Union (1360C>T) (2/19), which originated from the Oceania, was also detected. These findings suggest that the Kinh people are derived from various ancestries from continental Southeast Asia, China, and Oceania. In contrast, all of the 5 deficient cases in the K'Ho population were G6PD Viangchan, suggesting that they were very close to Southeast Asian populations such as the Khmer in Cambodia and the Lao in Laos. It is interesting that G6PD Mahidol (487G>A), another common variant in continental Southeast Asian populations in Myanmar, Thailand, and Malaysia, has not been detected from the Vietnamese.

Sequence variation in the T-cell epitopes of the Plasmodium falciparum circumsporozoite protein among field isolates is temporally stable: a 5-year longitudinal study in southern Vietnam.

In an effort to decipher the nature and extent of antigen polymorphisms of malaria parasites in a setting where malaria is hypomesoendemic, we conducted a 5-year longitudinal study (1998 to 2003) by sequencing the Th2R and Th3R epitopes of the circumsporozoite protein (CSP) of 142 Plasmodium falciparum field isolates from Bao Loc, Vietnam. Samples were collected during the high-transmission season, September through December 1998 (n = 43), as well as from July 2000 to August 2001 (n = 34), September 2001 to July 2002 (n = 33), and August 2002 to July 2003 (n = 32). Marked sequence diversity was noted during the high-transmission season in 1998, but no significant variation in allele frequencies was observed over the years (chi(2) = 70.003, degrees of freedom = 57, P = 0.116). The apparent temporal stability in allele frequency observed in this Bao Loc malaria setting may suggest that polymorphism in the Th2R and Th3R epitopes is not maintained by frequency-dependent immune selection. By including 36 isolates from Flores Island, Indonesia, and 19 isolates from Thaton, Myanmar, we investigated geographical patterns of sequence polymorphism for these epitopes in Southeast Asia; among the characterized isolates, a globally distributed variant appears to be predominant in Vietnam (75 of 142 isolates, or 52.8%) as well as in Myanmar (15 of 19 isolates, or 78.9%) and Indonesia (31 of 36 isolates, or 86.1%). Further analyses involving worldwide CSP sequences revealed distinct regional patterns, a finding which, together with the unique mutations observed here, may suggest a possible role for host or local factors in the generation of sequence diversity in the T-cell epitopes of CSP.

Adiponectin and glucose production in patients infected with Plasmodium falciparum.

Infections are often complicated by an increase in glucose production due to stimulation of the secretion of glucose counter-regulatory hormones and cytokines. Adiponectin, a fat-derived hormone with insulin-sensitizing properties, could play a regulatory role in the degree of stimulation of glucose production by the infectious agent. Therefore, we investigated the possible correlation between glucose production and plasma adiponectin levels in 25 subjects: 7 patients with cerebral malaria, 6 with uncomplicated malaria, and 12 matched controls. Glucose production was significantly higher in patients with malaria compared to healthy controls (P < .001). Adiponectin levels were not different between the patients with malaria and the control group. However, patients with cerebral malaria had significantly higher values for adiponectin than the patients with uncomplicated malaria (P < .005). Glucose production and gluconeogenesis were positively correlated to plasma adiponectin in the patients (r = 0.835, P < .001 and r = 0.846, P < .001, respectively), whereas these correlations were absent in the controls (r = -0.329, NS and r = -0.028, NS, respectively). In conclusion, adiponectin levels were not different between patients with malaria and their matched controls. However, patients infected with Plasmodium falciparum who have higher glucose production also have higher adiponectin levels. In healthy subjects such a correlation was not found. As adiponectin is known to inhibit glucose production, stimulation of adiponectin secretion during infection could be intended to restrain the glucose production stimulating properties of hormones and cytokines secreted during infection.

FFAs are not involved in regulation of gluconeogenesis and glycogenolysis in adults with uncomplicated P. falciparum malaria.

In normal subjects, elevation of plasma free fatty acid (FFA) levels stimulates gluconeogenesis (GNG) and inhibits glycogenolysis (GLY). In adults with uncomplicated Plasmodium falciparum malaria, GNG is increased and GLY decreased. To test the hypothesis that FFAs are regulators of GNG and GLY in uncomplicated falciparum malaria, we investigated the effect of inhibition of lipolysis by acipimox in 12 patients with uncomplicated falciparum malaria. Six of them were given acipimox, and six served as controls. Also as controls, six matched healthy subjects were studied on two occasions with and without acipimox. After 16 h of fasting, glucose production and GNG were significantly higher in the malaria patients compared with the healthy controls (P = 0.003 and < 0.0001, respectively), whereas GLY was significantly lower (P < 0.001), together with elevated plasma concentrations of cortisol and glucagon. During the study, glucose production in patients declined over time (P < 0.0001), without a statistically significant difference between the acipimox-treated and untreated patients. In controls, however, with acipimox the decline was less outspoken compared with nontreated controls (P = 0.005). GNG was unchanged over time in patients as well as in healthy controls, and no influence of acipimox was found. In patients, GLY declined over time (P < 0.001), without a difference between acipimox-treated and untreated patients. In contrast, in controls treated with acipimox, no change over time was found, which was statistically different from the decline in untreated controls (P = 0.002). In conclusion, in falciparum malaria, FFAs are not involved in regulation of glucose production, nor of GNG or GLY.

Influence of prolonged starvation on glucose kinetics in pregnant patients infected with Plasmodium falciparum.

Hypoglycaemia is a recognised complication of malaria in pregnancy, but its pathophysiology is not well understood. We studied the influence of fasting on glucose production and gluconeogenesis by infusion of [6,6-(2)H(2)]glucose and ingestion of (2)H(2)O in 20 female subjects, eight pregnant patients with uncomplicated falciparum malaria, six pregnant controls matched for age and trimester and six non-pregnant controls matched for age. Infection with Plasmodium falciparum induced a significant increase in glucose production (16.7+/-0.3 vs. 12.4+/-0.8 micromol/kg/min; P=0.002) and gluconeogenesis (12.5+/-0.6 vs. 8.2+/-0.7 micromol/kg/min; P=0.001) without a change in the glucoregulatory hormone milieu, compared to the healthy pregnant controls. Extension of the fast from 20.30 to 24.30 h resulted in a rate of decline of glucose production that was similar in patients with malaria and healthy pregnant subjects, a decline that was steeper compared to the non-pregnant subjects (-0.283 and -0.426 vs. -0.065 micromol/kg/min/h; P=0.037). The plasma glucose concentration measured at 20.30 h of fasting in the malaria patients was intermediate between the value found in the pregnant and the non-pregnant controls (4.01+/-0.2 mmol/l) while it was significantly lower in the non-infected pregnant women compared to non-pregnant controls (3.59+/-0.14 vs. 4.70+/-0.29 mmol/l; P=0.009). Plasma glucose concentration declined at a similar rate in patients with malaria and pregnant controls but faster compared to the non-pregnant controls (-0.078 and -0.093 vs. -0.044 mmol/l/h; P < 0.05). We conclude that fasting is a major risk factor for hypoglycaemia in pregnancy. Non-severe Plasmodium falciparum infection in pregnant women results in higher glucose production and higher glucose levels, thereby, compared to healthy pregnant patients, delaying of the occurrence of hypoglycaemia due to fasting. The exact mechanism of hypoglycaemia in fasting pregnant women remains to be elucidated.