Glucose-6-phosphate dehydrogenase (G6PD) mutations in Thailand: G6PD Viangchan (871G>A) is the most common deficiency variant in the Thai population.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common hereditary disorder in humans. Through a population study for G6PD deficiency using a cord blood quantitative G6PD assay in Bangkok, Thailand, we found that the prevalence of G6PD deficiency is 11.1% in Thai male (N=350) and 5.8% in female (N=172) cord blood samples. Among the neonates with hyperbilirubinemia, the prevalence of G6PD deficiency is 22.1% in males (N=140) and 10.1% in females (N=89). We developed a PCR-restriction enzyme-based method to identify G6PD Viangchan (871G>A), and searched for this and 9 other mutations in DNA from G6PD deficient blood samples. G6PD Viangchan (871G>A) was the most common mutation identified (54%), followed by G6PD Canton (1376G>T; 10%), G6PD Mahidol (487G>A; 8%), G6PD Kaiping (1388G>A; 5%), G6PD Union (1360C>T; 2.6%) and "Chinese-5" (1024C>T; 2.6%). Among 20 neonates with hyperbilirubinemia, G6PD Viangchan was also most frequently identified (60%), followed by G6PD Canton (10%), G6PD Mahidol, G6PD Union, and G6PD Kaiping (5% each). G6PD Viangchan appears from this study to be the most common G6PD mutation in the Thai population, bringing into question previous reports that G6PD Mahidol is most prevalent. G6PD Viangchan, together with G6PD Mahidol and G6PD Canton, are responsible for over 70% of G6PD deficiency in this study of Thais. With the data from other Southeast Asian ethnic groups such as Laotians, G6PD Viangchan (871G>A) is probably the most common variant in non-Chinese Southeast Asian population.

The value of methemoglobin reduction test as a screening test for neonatal glucose 6-phosphate dehydrogenase deficiency.

UNLABELLED: Glucose 6-phosphate dehydrogenase (G-6-PD) deficiency is common in the Thai population and is the cause of neonatal hyperbilirubinemia and hemolytic anemia. This X-linked disorder is much more common in males than females. The objectives of this study were to compare the result of the screening methemoglobin reduction test (MRT) with the gold standard G-6-PD activity, and also to determine the prevalence of G-6-PD deficiency in the cord blood and blood of neonates with hyperbilirubinemia. Five hunderd and twenty two randomly selected cord blood (350 males, 172 females) and 229 peripheral blood from neonates with hyperbilirubinemia were assayed for G-6-PD enzyme activity using a WHO-recommended standard test as well as methemoglobin reduction (MR) test. The results showed that prevalence of G-6-PD deficiency from the cord blood was 11.1 per cent in males, and 5.59 per cent in females. Among newborns with neonatal jaundice, the prevalence of G-6-PD deficiency was 22.1 per cent in males and 10.1 per cent in females. MRT in cord blood G-6-PD deficiency screening had acceptable sensitivity (85.7%) and high specificity (98.1%). The sensitivity of MRT in jaundiced infants was low (60.0%) whereas the specificity was acceptable (92.1%). The negative predictive values were more than 90 per cent while the positive predictive values were low (61-65%) from both specimens. CONCLUSIONS: G-6-PD deficiency is common in the Thai population, both in males and females and can be screened from cord blood by using low cost MRT. G-6-PD deficiency contributes to 20 per cent of neonatal jaundice, and screening with MRT yields low sensitivity.

Comparison study of combined DTPw-HB vaccines and separate administration of DTPw and HB vaccines in Thai children.

The safety, immunogenicity and tolerability of two different DTPw-HBV combination vaccines, containing 5 and 10 microg of HBsAg; were investigated in comparison with separate administration of DTPw and HBV (10 microg of HBsAg). A three dose primary vaccination course at 2, 4 and 6 months of age was followed by a booster dose at 18 months. All vaccines were safe and well tolerated. The DTPw-HBV combination vaccine containing 10 microg of HBsAg elicited significantly higher anti-HBs titres than the other two vaccines after the primary and booster vaccination course. All vaccines elicited a high response against the other components. Based on these results, DTPw-HBV (10 microg HBsAg) was the most effective vaccine at this schedule.

Molecular analysis of the a determinant of HBsAg in children of HBeAg-positive mothers upon failure of postexposure prophylaxis.

OBJECTIVE: To investigate the a determinant of hepatitis B virus (HBV) S gene for the presence of mutations responsible for vaccine failure. METHODS: The a determinant of HBV S gene was amplified in sera obtained from 11 HBV-positive infants and children born to asymptomatic HBeAg-positive mothers by nested polymerase chain reaction (PCR) and subsequently subjected to direct sequencing. The sequences obtained were translated into the corresponding amino acids and compared to amino acid sequences of HBV subtype adr. All infants under investigation had received recombinant hepatitis B vaccine within 24 hours after delivery and had completed the recommended vaccination course, consisting of three to four doses administered at defined intervals. RESULTS: The usual divergence regarding genotype and subtype was identified among the 11 samples tested. Only two exhibited a point mutation within the a determinant, one of which consisted of a substitution of glycine with alanine at position 145, and the other of a substitution of glutamine with arginine at position 129. CONCLUSION: Eleven neonates were positive for HBV infection, and two of them showed point mutations that might have rendered the virus resistant to the vaccine, possibly due to a change in the S protein's secondary structure. Yet, this remains a matter of speculation, since the other seven cases positive for hepatitis B viral DNA merely demonstrated the usual genotype and subtype. The presence of escape mutants of HBV can be considered rather negligible with respect to vaccination programs, especially as the vaccine has been shown to reduce hepatitis B, as well as hepatocellular carcinoma efficiently.

Long-term hepatitis B vaccine in infants born to hepatitis B e antigen positive mothers.

Neonates of hepatitis B surface antigen (HBsAg) positive and hepatitis B encoded antigen (HBeAg) positive mothers received 10 micrograms of recombinant hepatitis B vaccine at months 0, 1, 6, or 0, 1, 2, 12, with or without immunoglobulin at birth, and were followed up to the age of 8 years for HBsAg, anti-HBc, and anti-HBs. Some were boosted at month 60. The overall vaccine protection at month 12 was 96.2%. No child became a chronic carrier beyond the age of 3 years, showing that this vaccine provides immediate protection against HBsAg carriage, and long term protection against fetally acquired HBsAg. After month 60 hepatitis B serological markers without disease, indicating re-exposure to HBV, reappeared in comparable numbers among boosted and non-boosted children (5 for a total of 167 children). This vaccine provides long-term protection against hepatitis B chronic carriage and infection in high risk neonates with or without a month 60 booster. A booster at the age of 5-6 years or 11-12 years would reduce HBV infection, viral circulation and transmission, while ensuring long-term antibody persistence.

Long-term antibody persistence after booster vaccination with combined tetravalent diphtheria tetanus, whole-cell Bordetella pertussis and hepatitis B vaccine in healthy infants.

Combining HB vaccine with routine paediatric vaccines has been recognized as the best means of universal vaccination against hepatitis B. Our objective was to evaluate the long-term antibody persistence of such a combined vaccine in an area of high hepatitis B endemicity. We have shown that a DTPw-HB vaccine was safe and immunogenic when given as a booster dose at 18 months of age. One month after the booster dose of DTPw-HB vaccine, at least 97.8% of subjects had seroprotective anti-HBsAg levels, and 1 year later at least 93.9% of these subjects remained seroprotected against HBsAg. Immune responses to the DTPw components were similar or greater than those of the commercial DTPw vaccine given to the control group. This DTPw-HB vaccine, which showed good long-term anti-HBsAg antibody persistence, could advantageously replace separate DTPw and HB vaccines in areas of high hepatitis B endemicity in terms of clinical, economic and strategic benefits.

Immunogenicity of hepatitis B vaccine in premature infants.

The immunogenicity of plasma-derived hepatitis B vaccine was studied in 39 premature neonates, whose weights were 1,800-2,400 g and gestational ages 32-37 weeks. All maternal antiHBc antibody were negative. Dosage of 5 micrograms of hepatitis B vaccine (Pasteur vaccine) was given at 0, 1, 2 and 12 months after birth. At the ages of 1, 2, 4, 9, 12 and 13 months, antiHBs antibody was found in 7.7%, 20%, 69.7%, 81.4%, 77.3% and 89.5%, respectively, while the geometric mean titer in this seropositive group, starting at age 2 months was 37, 121, 113, 69 and 1,016 mIU/ml. There was no severe reaction attributed to the vaccination. The result indicated that the vaccine was immunogenic. Although the conversion rate was low after primary injection, a satisfactory response developed at age 4 months after 3 doses of vaccine.

Long term efficacy of hepatitis B vaccine in infants born to hepatitis B e antigen-positive mothers.

The long term protective efficacy of recombinant hepatitis B vaccine, administered alone or concomitantly with hepatitis B immunoglobulin, was assessed in 263 healthy neonates of hepatitis B e antigen-positive mothers. Infants received the first dose of vaccine at birth; additional doses were given at either Months 1, 2 and 12 or Months 1 and 6. During the follow-up period, which ranged from 2 to 4 years, protective titers (> or = 10 mIU/ml) of anti-hepatitis B surface antibodies were found in virtually all infants who had responded to the primary course of vaccination. "Natural boosts," without persistent infection, were observed in only a small number of children. All children who were shown to have become chronic carriers were infected within the first year of life. No statistical difference in long term protective efficacy could be shown between the two vaccination schedules used or between the use of vaccine alone or vaccine plus hepatitis B immunoglobulin for either schedule.

Comparison of a recombinant DNA hepatitis B vaccine alone or in combination with hepatitis B immune globulin for the prevention of perinatal acquisition of hepatitis B carriage.

The protective efficacy of a recombinant DNA yeast-derived hepatitis B vaccine was assessed alone or in combination with hepatitis B immune globulin (HBIg) in neonates born to surface antigen (HBsAg)-positive and e antigen (HBeAg)-positive mothers. Neonates received either a 10 micrograms dose of vaccine alone or the same dose of vaccine plus 0.5 ml HBIg within 12 h of birth. All infants subsequently received 10 micrograms of vaccine at 1, 2 and 12 months. Only two of the 58 (3.4%) newborns of HBsAg-positive/HBeAg-positive mothers receiving vaccine alone became chronically infected with hepatitis B virus (HBV) while all infants administered vaccine + HBIg were protected. These results indicate that although the administration of HBIg can increase the protection rate, the use of vaccine without concomitant administration of HBIg according to the above schedule could considerably reduce the risk of perinatal HBV transmission.

Protective efficacy of a recombinant DNA hepatitis B vaccine in neonates of HBe antigen-positive mothers.

We have assessed the protective efficacy of a recombinant DNA hepatitis B vaccine alone in infants of women who were positive for the surface antigen and the e antigen. The infants received a 10-micrograms dose of the vaccine within 12 hours of birth and additional doses 1, 2, and 12 months later. No significant adverse reactions to vaccination were observed and the vaccine was highly immunogenic. Only 2 (3.6%) of the 55 infants followed up to 13 months became chronically infected with the hepatitis B virus, as evidenced by the persistent presence of hepatitis B surface antigen in serum samples. Without immunoprophylaxis, 65% to 90% of such infants would become chronic carriers. Immunization with a recombinant vaccine without concomitant administration of hepatitis B immunoglobulin, therefore, considerably decreased the incidence of the carrier state.