We aimed to investigate the influence of regulatory T cells including CD4+CD25+, CD8+CD28- and hepatitis B virus (HBV) genotype on sustained virological response and tolerance of nucleoside drugs. One hundred and thirty-seven patients were enrolled. Lamivudine was administered to 84 patients. Entecavir was administered to the other 53 patients. Before treatment, biochemical tests, HBV DNA load, HBV serum level, HBV genotype, PB CD3+, CD4+, CD8+, CD4+CD25+/CD3+, and CD8+CD28-/CD3+ frequencies were measured. Based on HBV DNA loads after 4 weeks of therapy, patients were divided into response group and suboptimal response group. The lamivudine group received treatment continuously, and then patients were categorized into non-resistance group and resistance group. Compared with the suboptimal response and resistance groups for lamivudine, CD4+CD25+/CD3+ levels were higher in the response and non-resistance groups (t=4.372, P=0.046; t=7.262, P=0.017). In the non-resistance group, CD8+CD28-/CD3+ frequency was lower than in the resistance group (t=5.527, P=0.037). Virus load and hepatitis B E antigen (HBeAg)-positive rate were significantly lower than in the response and resistance group (t=2.164, P=0.038; X2=4.239, P=0.040; t=2.015, P=0.044; X2=16.2, P=0.000). Incidence of drug resistance was high in patients with virogene type C. For the virological response to entecavir, CD8+CD28-/CD3+ level was significantly lower than that of the suboptimal response group (t=6.283, P=0.036). Response and suboptimal response groups were compared in CD3+, CD4+, CD8+, CD4+CD25+/CD3+ and virus genotype, and differences were not statistically significant (P>0.05). Baseline regulatory T cells including CD4+CD25+/CD3+ and CD8+CD28-/CD3+ frequencies have a relationship with the incidence of rapid virological response and the resistance to nucleoside drugs. Patients with HBV genotype C receiving lamivudine more often underwent drug resistance. Antiviral efficacy and the resistance to lamivudine were closely correlated with baseline factors; the same cannot be found for entecavir.

OBJECTIVE: To test the efficacy of locally produced Vi vaccine over a time period of longer than one year. METHODS: A double-blinded, randomized field trial was performed in Guangxi Zhuang Autonomous Region in south-western China, using 30 mg doses of locally produced Vi. Enrolled subjects were 3-50 years of age, although the majority (92%) were school-aged children, who have the highest rate of typhoid fever in this setting. A total of 131 271 people were systematically allocated a single dose of 30 mg of Vi polysaccharide or saline placebo. The study population was followed for 19 months, with passive surveillance conducted in the Ministry of Health and the Regional Health and Anti-epidemic Centre (HAEC). Clinically suspected cases of typhoid fever were confirmed by blood culture, or by serological reaction with O-antigen (Widal tests). FINDINGS: After 19 months, there were 23 culture-confirmed cases of typhoid fever in the placebo group versus 7 cases in the Vi group (Protective efficacy (PE) = 69%; 95% CI = 28%, 87%). Most of the isolates were from school-aged children: 22 cases in the placebo group versus 6 in the Vi group (PE = 72%; 95% CI = 32%, 82%). No serious post-injection reactions were observed. The locally produced Vi polysaccharide vaccine showed levels of protective efficacy similar to those for Vi vaccine produced in industrial countries. CONCLUSION: The slightly higher dose of vaccine did not seem to alter efficacy significantly in China.

OBJETIVO: Determinar la eficacia de la vacuna de Vi producida localmente a lo largo de un periodo superior a un año. MÉTODOS: Se llevó a cabo un ensayo sobre el terreno aleatorizado y en doble ciego en la región autónoma (provincia) de Guangxi Zhuang, en el suroeste de China, usando dosis de 30 mg de la vacuna Vi producida localmente. El intervalo de edades de las personas participantes era de 3-50 años, si bien la mayoría de ellas (92%) eran niños en edad escolar, los más afectados por la fiebre tifoidea en ese lugar. Se asignó de forma sistemática a un total de 131 271 personas para que recibieran ya fuera una dosis única de 30 mg de polisacárido Vi o bien un placebo constituido por suero fisiológico. La población estudiada fue objeto de seguimiento durante 19 meses, y la vigilancia pasiva corrió a cargo del Ministerio de Salud y del Centro Regional de Salud y Lucha contra las Epidemias (HAEC). Los casos con manifestaciones clínicas sugestivas de fiebre tifoidea fueron confirmados mediante cultivo sanguíneo o mediante la reacción serológica con el antígeno O (pruebas de Widal). RESULTADOS: Al cabo de 19 meses se habían confirmado mediante cultivo 23 casos de fiebre tifoidea en el grupo placebo, frente a 7 casos en el grupo tratado con la vacuna Vi (eficacia protectora (EP) = 69%; IC95% = 28-87%). La mayoría de los aislados correspondían a niños en edad escolar: 22 casos en el grupo placebo, frente a 6 en el grupo tratado con Vi (EP = 72%; IC95% = 32-82%). No se observó ninguna reacción grave postinyección. La vacuna basada en el polisacárido Vi producida localmente demostró tener una eficacia protectora similar a la de la vacuna Vi producida en los países industrializados. CONCLUSIÓN: El ligero aumento de la dosis de vacuna no parece haber influido de forma significativa en su eficacia en China.

OBJECTIF:Tester l’efficacité du vaccin antityphoïdique polyosidique Vi de production locale sur une période de plus d’un an. MÉTHODS: Un essai de terrain randomisé en double aveugle a été réalisé dans la région autonome (province) de Guanxi Zhuang dans le sud-ouest de la Chine, au moyen de doses de 30 mg de polyoside Vi de production locale. Les sujets recrutés dans l’étude étaient âgés de 3 à 50 ans, mais étaient pour la plupart (92 %) des enfants d’âge scolaire, groupe qui présente le taux le plus élevé de fièvre typhoïde dans cette région. Au total, 131 271 personnes ont reçu systématiquement une dose unique de 30 mg de polyoside Vi ou un placebo (soluté physiologique). La population d’étude a été suivie pendant 19 mois dans le cadre d’une surveillance passive exercée par le Ministère de la Santé et le Centre régional de la santé et de la lutte contre les épidémies (HAEC). Les suspicions cliniques de fièvre typhoïde ont été confirmées par hémoculture ou par réaction sérologique en présence d’antigène O (test de Widal). RÉSULTATS: Au bout de 19 mois, on a dénombré 23 cas de fièvre typhoïde confirmés par culture dans le groupe placebo contre 7 cas dans le groupe Vi (efficacité protectrice (EP) = 69% ; intervalle de confiance à 95% (IC 95 %) : 28-87 %). La plupart des isolements ont été réalisés chez les enfants d’âge scolaire, avec 22 cas dans le groupe placebo contre 6 cas dans le groupe Vi (EP = 72%; IC 95%: 32-82 %). Aucune réaction grave n’a été observée après l’injection. Le vaccin polyosidique Vi de production locale a montré des taux d’efficacité protectrice similaires à ceux des vaccins produits dans les pays industrialisés. CONCLUSION: La dose légèrement plus forte de vaccin n’a pas semblé modifier l’efficacité de fac¸on significative en Chine.