Access to medicines in Senegal: results of a sample survey.

The survey was conducted in Senegal in April 2001 on a representative sample of providers and clients. Results show that access to medicines in Senegal was limited for three main reasons: (1) the supply of drugs was inadequate, and even critical drugs were often missing in health centres, and were somewhat less in pharmacies; (2) the health infrastructures appeared insufficient to cover the needs of the whole population, creating high opportunity costs; (3) the cost of the drugs prescribed was higher than the minimum price, sometimes exceeding the capacity of poorer people, although high cost was seldom reported as the main reason for not acquiring prescribed drugs. Improving access to medicine is a priority to help reduce health inequalities in developing countries.

[A new combined vaccine against yellow fever and measles in infants aged 6 to 24 months in Mali]. / Etude d'un noveau vaccin combiné contre la fièvre jaune et la rougeole chez des enfants agés de 6 a 24 mois au Mali.

In a rural area in Mali, 453 children were randomly enrolled in a study comparing the safety and the immunogenicity of a combined yellow-fever-measles freeze dried vaccine with each yellow-fever and measles separate administration. Children were divided in 2 populations 4-8 and 12-24 month old. 249 were controlled for measles (inhibition of hemagglutination) and yellow-fever (seroneutralization) antibodies. Seroconversion rates for measles were 82% when administrated before 9 months and 100% when given in 12-24 months period. Measles GMT is similar whatever the schedule or the age group; so, early vaccination does not impair the immunogenetic response. Moreover, 96% of the children vaccinated before 9 months still have detectable measles protective antibodies 8 months after. Among the initially seronegative children, the yellow-fever response is satisfactory with 92 to 96% seroconversion rate and post-immunization GMT ranging 16.5 to 29.5 without any statistical difference between the vaccine and age groups. The safety of the combined yellow-fever-measles vaccine is assessed by the rare number of reactions which are equivalent with the normally expected reactions with each vaccine administered separately. The results demonstrate the satisfactory immunogenicity and safety of the combined yellow-fever-measles vaccine. Combine yellow-fever-measles vaccination could help to improve the feasibility of EPI.

[The combined measles-yellow fever vaccination in African infants aged 6 to 10 months]. / Etude de la vaccination combinée rougeole-fièvre jaune chez l'enfant African âgé de 6 à 10 mois.

The compared tolerance and immunogenicity of vaccines against yellow fever and measles, separately administered or combined, have been evaluated in a group of 319 children from North Cameroon, aged 6-10 months. The clinical tolerance was excellent for both the isolated and the combined vaccines. The seroconversion level is higher after administration of the combined vaccine: 89.9% against 83.5% for measles, 95.8% against 92.6% for yellow fever, but these results are not significantly different. 30 days after vaccination, the antibody titers are higher with the combined vaccine: 215.3 against 156.5 for measles (non significant difference), 34 against 22.6 for yellow fever (highly significant difference). Whatever the vaccination method is, the antibody levels are protecting. It becomes then possible to include the combined vaccination against yellow fever and measles in the EPI of yellow fever endemic countries.

[Rabies in France, 100 years after Pasteur]. / La rage en France, 100 ans après Pasteur.

Pasteur's vaccination, a huge step forward in infectiology, remains the fundamental element in the fight against rabies. Since 1968, when rabid foxes reappeared in France there have been no domestic cases of human rabies, but from 1970 to 1993, 14 patients contaminated in enzootic areas (usually Africa) died from rabies in France. The new circulation conditions created by the European Union emphasizes the importance of the inactivated Pasteur vaccine cultivated on Vero cell lines. The classic protocol for post-exposure vaccinations is based on 5 intramuscular injections on day 0, 3, 7, 14 and 30. In 1988, the World Health Organization established new recommendations: the 2-1-1 schedule for post-exposure vaccination. Two injections are given on day 0 at two different sites followed by boosters on day 7 and day 21. Tested worldwide by independent laboratories, this schedule has been shown to effectively induce seroconversion when modern cell-culture vaccines are used. Although there is still a certain amount of debate on the new schedule, no failures have been recorded. The Centers for Disease Control in Atlanta recommend preventive vaccination for exposed professions based on primary and booster injections on day 0, 7, 28 and 365. Protection lasts for 3 years and may be prolonged with supplementary vaccinations. One hundred years ago, Pasteur taught us that we could protect the human population by fighting against animal contamination. Today's progress is the reward of such foresight--and a challenge to both human and veterinary medicine.

Comparative trial of administration of half (0.05 mg) and quarter (0.025 mg) dose of intradermal Pasteur BCG on 291 infants from birth to 1 year in French Guyana.

The study concerns 291 newborns and infants aged 0 to 1 year placed randomly in two groups which respectively received 0.025 and 0.05 mg Pasteur BCG by intradermal injection, between 1 December 1988 and 28 February 1989. This random test aimed to determine if the administration of one quarter dose (0.025 mg) of intradermal BCG conferred immunity comparable to that of one half (0.05 mg) while diminishing the risk of complications, in particular suppurative adenopathy, in infants of ages 0-1 year. Statistical analysis of the results showed that the 0.025 mg dose of intradermal BCG entails an immunoresponse as satisfactory as that entailed by the 0.05 mg dose, while the rate of suppurative adenitis is significantly higher in the group that received the 0.05 mg dose. It is therefore well justified to recommend a dose of 0.025 mg of intradermal Pasteur BCG for infants aged 1 year and less.

Combined vaccination against yellow fever and typhoid fever: a comparative trial.

In order to evaluate a combination of yellow fever and typhoid fever vaccine, we conducted a controlled trial comparing reactogenicity and immunogenicity of Vi polysaccharide (ViPS) vaccine and yellow fever 17D (YF) vaccine after single, simultaneous and combined administration. The combined YF/ViPS vaccine was prepared by using the liquid ViPS vaccine as a diluent for the YF vaccine. The stability of such a reconstitution had been assessed in vitro. Safety was evaluated using a self-surveillance form and by repeated clinical visits. Immunogenicity was evaluated by a plaque reduction test for YF and by radioimmunoassay for ViPS. Tolerability was satisfactory in all groups. There was no increase in local or general reactions in groups receiving both vaccines, whether given simultaneously or combined. The serological response to ViPS was similar after single and simultaneous or combined administration. Interestingly, the immune response to YF was significantly enhanced in groups receiving the vaccines simultaneously or combined, suggesting a potential adjuvant effect of ViPS.

Comparison of the safety and immunogenicity of the lyophilized Mérieux seed and the World Health Organization working reference BCG vaccines in school-aged children in Senegal.

In order to validate two new lots of Mérieux BCG vaccine (Mérieux seed derived from strain 1072), a calibration study was performed to compare their safety and immunogenicity to a full dose of the WHO-reference BCG vaccine (Tokyo strain 172) as well as the WHO-reference vaccine given at 1/10 of its normal concentration, in an open, randomized, four-arm, multicenter study in Senegal. A total of 1041 healthy Senegalese children aged 8-10 years were screened for participation in this study, of whom 548 had a negative Mantoux test and complied with inclusion and exclusion criteria. These children were randomly allocated a single dose of one of the following vaccines: full-dose Mérieux BCG vaccine (lot E0650); full-dose Mérieux BCG vaccine (lot E0624); full-dose WHO-reference vaccine (Tokyo strain 172); or 1/10 dose WHO-reference vaccine. A follow-up examination, including a tuberculin test, was performed 10-12 weeks after BCG vaccination for 465 (85%) children: 236 Mérieux BCG vaccine (117 lot E0650; 119 lot E0624); 115 full-dose WHO; 114 1/10 dose WHO. The percentage of subjects with a positive tuberculin test after vaccination was significantly lower (P < 0.001) in the 1/10 dose group (81.5%) compared to the other three groups (> 96%). The mean induration diameter was significantly smaller in subjects who received the low-dose of WHO vaccine compared to the others, according to analyses considering all subjects vaccinated, as well as only those subjects with a positive tuberculin test after vaccination. More children in the low-dose group did not have a vaccination scar, and the mean diameter of scars was smaller in this group. The rate of tuberculin reactions, the classification of reactions (Palmer and Edwards), and the characteristics of the vaccinal lesion were similar for the Mérieux BCG vaccines and the full-dose WHO-reference vaccine. All vaccines were safe, as evidenced by the absence of adenitis or suppurative adenitis during the course of the study. Results from this trial show that the two lots of Mérieux BCG vaccine behave equally as well as the full-dose WHO-reference BCG vaccine. The WHO-reference vaccine, given at 1/10 of its normal concentration was significantly less immunogenic, according to all parameters evaluated.

Safety and immunogenicity of combined rabies and typhoid fever immunization.

The prevalence of rabies and typhoid fever in many developing countries poses a serious health hazard to travellers. The development of a combined immunization schedule would be advantageous. A study was performed on 104 adult volunteers using purified Vero cell rabies vaccine and Typhim Vi, a purified capsular polysaccharide, either separately or in combination. No significant difference was observed in immunogenicity or tolerance between the two groups. A 3-year follow-up study is planned.

[Infection of insect cell lines by the HIV virus, an agent of AIDS, and a demonstration of insects of African origin infected by this virus]. / Infection de cellules d'insectes en culture par le virus HIV, agent du SIDA, et mise en évidence d'insectes d'origine africaine contaminés par ce virus.

The etiological agent of AIDS known as HIV has been shown to bind on different insect cell lines including Drosophila, Mosquito, Ceratitis; and his DNA to be integrated in the cellular genome, but no expression of the viral genome was detected in those cells. None of the human lymphocytes markers is expressed at the surface of the insect cells. HIV proviral DNA has been also found in various insects from Central Africa (Zaïre and Central Africa Republic) but not similar insects from the Paris area. These data suggest that insects could be a reservoir or a vector for the AIDS virus.

Simultaneous injection of hepatitis B vaccine with BCG and killed poliovirus vaccine.

In most developing countries, hepatitis B virus is endemic and prevention has to be carried out early in life and on a mass scale. In these regions, simultaneous administration of multiple antigens is normal practice. We have therefore investigated the interaction of hepatitis B vaccine with BCG and inactivated polio vaccine. The serological antibody response to poliovirus and HBsAg as well as the cellular immune response to tuberculin post BCG immunization were assessed. The immune responses to HBsAg, BCG and polio vaccines injected simultaneously were comparable to those observed after separate administration of each vaccine. Moreover, no increase of adverse reactions was noted. Results confirmed that HB vaccine could be introduced into the WHO expanded programmes on immunization without impairing the expected protective efficacy against the targeted vaccine-preventable diseases.