Simultaneous injection of plasma-derived or recombinant hepatitis B vaccines with yellow fever and killed polio vaccines.

Previous studies have shown an absence of interaction between hepatitis B (HB) vaccine and other vaccines used in EPI programmes except for an apparent decrease of yellow fever antibody levels when hepatitis B and yellow fever vaccines are given simultaneously. We have therefore reinvestigated the interaction of these two vaccines and assessed the absence of interaction between inactivated polio vaccine and recombinant or plasma-derived HB vaccine. The immune responses to polio vaccine injected simultaneously with plasma-derived or recombinant HB vaccine were observed to be equivalent and similar to those observed in the literature. In this randomized study, the immune responses to yellow fever injected simultaneously with plasma-derived or recombinant HB vaccine were comparable to those observed after separate administration of each vaccine. Moreover, no increase in adverse reactions was noted.

Twelve-year follow-up study of hepatitis B immunization of Senegalese infants.

Numerous studies have documented the efficacy and safety of plasma-derived and recombinant hepatitis B vaccines. However, little is known about the long-term protection of hepatitis B vaccine, when anti-HBs declines to low or undetectable levels. This study reports results from a 9-12-year period follow up of infants immunized against hepatitis B in Senegal. At the end of the follow-up period anti-HBs were detected in 81% of children who received a booster dose at school age and in 68% of those who did not. HBsAg was detected in 19% of infants from the control group compared to only 2% of immunized infants, corresponding to a protective efficacy of 88%. The results show that long-term protection against HBsAg carriage of hepatitis B vaccination is very high and that a booster dose at school age does not significantly increase this protection.

Scheduling of revaccination against hepatitis B virus.

Studies have shown that to maintain protection against infection after a primary course of hepatitis B immunisation, revaccination can be scheduled on the basis of an anti-hepatitis B virus surface antigen (anti-HBs) titre obtained 1 month after the booster dose. However, schemes which require post-booster testing may present practical difficulties. We applied a random-effects regression model to data from 118 Senegalese infants given three injections of hepatitis B vaccine about 6 weeks apart and a booster injection at 13 months, and show that revaccination can be scheduled on the basis of an anti-HBs titre recorded at the time of the booster dose. We also show that titre-at-booster is no less accurate in predicting future titre than 1-month post-booster titre. In several other studies the post-booster decline in anti-HBs conforms to the same mathematical description, indicating the generality of our findings.

Antibody response to preS1 in hepatitis-B-virus-induced liver disease and after immunization.

Antibodies to the pre-S1-encoded sequence of hepatitis B virus (HBV) envelope were detected by ELISA using a synthetic peptide analogue of preS1 proteins, in different groups of HBV-infected subjects and also in hepatitis B vaccine recipients. Such antibodies were specifically found in only 1% of HBsAg chronic carriers including patients with cirrhosis and primary liver cancer. Anti-preS1 were detected in patients with acute hepatitis; in 13% of the HBsAg+ sera obtained before recovery and in 37% of the sera obtained after recovery. Anti-preS1 antibodies were detected in recipients of a plasma-derived vaccine, but not in those receiving a recombinant vaccine. The results indicate that anti-preS1 is an earlier serum marker of HBV clearance than anti-preS2 and anti-S antibodies.

Prevalence of hepatitis C virus infection in Africa: anti-HCV antibodies in the general population and in patients suffering from cirrhosis or primary liver cancer.

Anti-hepatitis-C-virus (anti-HCV) antibody was tested for in sera from 410 adults living in Tunisia, Senegal, Burundi and Madagascar, and in 209 Tunisian and Senegalese patients suffering from liver diseases. Anti-HCV antibodies were detected in 4.2% of the adult population from Africa, in 51% of patients suffering from liver cirrhosis and in 37% of patients suffering from primary liver cancer. However, higher proportions of anti-HCV antibodies were detected in HBsAg+ patients than in HBsAg- patients. To assess the role of HCV in the development of both cirrhosis and primary liver cancer, a confirmation test is needed.

Hepatitis B surface antigen reactivity in man due to a new variant of hepatitis B virus.

A new type of hepatitis B virus (HBV) infection has been encountered in Senegalese infants and French adults characterized by serum hepatitis B surface antigen (HBsAg) without antibodies to the core antigen (anti-HBc). As the infection is not associated with the presence of the e antigen, it differs from HBV in its core antigen. After the loss of HBsAg, neither anti-HBc nor antibodies to HBsAg (anti-HBs) become detectable. This new infection (called HBV2 as opposed to the classical HBV1 infection) was found in infants with anti-HBs, either naturally acquired or produced by immunization against HBV. The use of monoclonal anti-HBs antibodies showed that two epitopes of HBV1 surface antigen could be detected in HBV2-positive sera. HBV DNA sequences could only be found in one of 15 HBV2-infected children using a DNA-DNA hybridization procedure; low levels of HBV DNA were also detected in 58% of the HBsAg-positive adult sera tested. If this new infection, apparently related to HBV1, is shown to cause chronic liver disease, hepatitis B vaccine should also contain surface antigen from HBV2.

Hepatitis B virus infection in lepromatous and tuberculoid patients from Senegal.

Hepatitis B Virus (HBV) seric markers (HBs Ag, anti-HBs, and HBe Ag) were studied in 987 Senegalese leprosy patients (lepromatous: LL; tuberculoid: TT) in comparison with 6187 healthy adults (controls). Two populations of leprosy patients from ILAD (Institut de Léprologie Appliquée de Dakar) were studied: The First study (i.e.: study I) between 1973 and 1977 included 553 patients (329 LL; 224 TT). The Second study (i.e.: study II) between 1982 and 1986 included 434 patients (236 LL; 198 TT). HBV serological markers were tested by various techniques. By RIA, they were present in 98% and 96.5% in the studies I and II respectively. Each marker was studied and compared to the control population. HBs Ag detected by RIA was present in 25.5% (study I) and 23.0% (study II) when comparing to 15.2% in the control group. This marker was correlated with leprosy forms (LL and TT), age, sex, ethnic group.

[Incidence of pathogenic Escherichia coli in acute infantile diarrhea in Dakar]. / Incidence des Escherichia coli pathogènes sur les diarrhées aiguës infantiles à Dakar.

We have studied the incidence of enteropathogenic (EPEC), enteroinvasive (EIEC) and enterotoxigenic (ETEC) Escherichia coli associated with infant acute diarrhoeal disease in Dakar during a period of one year. We report 405 strains of Escherichia coli suspected to be the etiologic agent of the diarrhoea and isolated from 405 diarrheic stools of 0-5 years old children. We have isolated 119 pathogenic Escherichia coli with 63 EPEC (15.5%), 3 ETEC (0.7%) and 53 ETEC (13.1%) including 23 strains releasing heat-labile enterotoxin (LT+) and 30 strains releasing heat-stable enterotoxin (ST+). No ST+/LT+ strain was isolated. Escherichia coli with colonization factor antigens were isolated from 62 children. Almost all of them are CFAI+. Only one strain is CFAII+ and another one agglutinates with both CFAI and CFAII antisera. Among these CFA+ strains 5 belong to the EPEC group, 29 are enterotoxigenic (25 ST+ and 4 LT+) and 28 do not belong to any known etiopathologic group. Near 70% of the pathogenic Escherichia coli are from infants less than one year old, with a highest frequency between 7 and 12 months. Prevalence of ETEC is higher during the raining season. The existence of a great number of strains that belong to none of the 3 groups of etiopathologic Escherichia coli emphasis the need to search other factors of pathogenicity.

HBsAG positive reactivity in man not due to hepatitis B virus.

A viral infection characterised by serum HBsAg positivity with serum anti-HBc negativity has been encountered in Senegal. The infection is not associated with the presence of HBeAg, so it differs from hepatitis B virus in its core antigen, but the surface antigen of the two viruses share some epitopes. After the loss of HBsAg, neither anti-HBc nor anti-HBs becomes detectable. Anti-HBs, naturally acquired or produced by immunisation, does not protect against this new infection. Chronic carriage occurs. If this new infection is confirmed to cause chronic liver disease, hepatitis B vaccine should include surface antigen from the new virus.

Hepatitis B vaccine in infants from an endemic area: long-term anti-HBs persistence and revaccination.

Persistence of anti-HBs in 156 Senegalese infants immunized with hepatitis B vaccine was studied for periods ranging from 2 to 6 years after booster dose administration. Six years after the booster dose, 90.4% of the infants had detectable anti-HBs antibodies, with 78.1% having titers higher than 10 mIU/ml. The geometric mean titer was 60 mIU/ml. Females showed higher anti-HBs values than males. In a group of 11 infants who received no booster dose, anti-HBs antibodies were detectable 7 years after the first dose. However, the geometric mean titer was lower (26 mIU/ml). Revaccination (56 infants) led to an increase of the geometric mean titer to 469 mIU/ml 2 months later. These results show that a booster injection every 5-6 years should provide adequate protective anti-HBs levels in infants.

Age- and sex-related study of hepatitis B virus chronic carrier state in infants from an endemic area (Senegal).

This report concerns hepatitis B virus (HBV) infections observed in 155 infants from Senegal, studied with a view to determining the factors involved in development of the chronic carrier state. A chronic carrier state was observed in 50.3% of the infants. This study confirms that the risk of chronic carriage is linked to age. This risk declines very rapidly with age, falling from 82% in infants under 6 months old, to 15% in children between the ages of 2 and 3 years. Spontaneous elimination of hepatitis B surface antigen (HBsAg) is uncommon in HBsAg carriers during childhood. The difference observed in chronic carriage between males and females is due to a difference in susceptibility of the two sexes to the development of the chronic carrier state: HBV infections (before 2 years of age) lead to a chronic carriage in 77% of males as against 50% of females. These conclusions are important in view of the immunisation programs being carried out against hepatitis B virus in endemic areas. For a maximum efficacy, vaccination must be carried out at birth, or shortly afterwards.

Seven-year study of hepatitis B vaccine efficacy in infants from an endemic area (Senegal).

A booster dose of hepatitis B vaccine was given to 143 children in whom hepatitis B had not developed 1 year after initial vaccination. Over the next six years the incidence of hepatitis B in this group was 1.5% per year compared with 11.5% per year in a similar group of unvaccinated children. In the first 4 years the protective efficacy of the vaccine was 100%, but during the 5th and 6th years it fell to 67%. For maximum protection a second booster is needed, 5 years after the first.

Simultaneous administration of hepatitis B and yellow fever vaccines.

In most developing countries, hepatitis B prevention is carried out early in life. In these countries, mobile immunization teams have a limited number of sessions to devote to each rural community; simultaneous administration of multiple antigens is thus normal practice. We compared the immune responses of Senegalese children to the separate or simultaneous injections of yellow fever and hepatitis B vaccines. Injections were given at the time of booster injection for hepatitis B vaccine. Yellow fever antibodies were detected in similar proportions in infants immunized with either yellow fever vaccine alone or yellow fever and hepatitis B vaccines simultaneously. However, a lower proportion of high yellow fever antibody levels were observed when the two vaccines were injected simultaneously. No reduction in the anamnestic response of antibodies against the surface antigen of hepatitis B virus (anti-HBs) was observed when yellow fever vaccine was injected at the same time as the booster dose of hepatitis B vaccine. Since no untoward reactions were noted, it is concluded that hepatitis B and yellow fever vaccines can be administered at the same time.

Simultaneous administration of diphtheria-tetanus-pertussis-polio and hepatitis B vaccines in a simplified immunization program: immune response to diphtheria toxoid, tetanus toxoid, pertussis, and hepatitis B surface antigen.

We studied the interactions of hepatitis B vaccine with other vaccines used in the World Health Organization expanded programs of immunization. Three groups of Senegalese children were vaccinated with hepatitis B vaccine (HB) alone, diphtheria-tetanus-pertussis (DTP)-polio vaccine alone, or a combination of hepatitis B vaccine and DTP-polio vaccines simultaneously. The immune responses to HBsAg, tetanus toxoid, diphtheria toxoid, and pertussis were measured after one and two vaccinations at 6-month intervals. The immune responses to the combination of HB vaccine and DTP-polio vaccines were similar to the immune responses observed after administration of each vaccine alone. In addition, no adverse reactions were noted. These experimental trials also demonstrated that with a DTP-polio vaccine containing 30Lf of tetanus and diphtheria toxoids, two doses given at 6-month intervals are sufficient to provide a satisfactory immune response. In the case of pertussis and HB vaccines; however, a third dose is necessary.