Tolerance and immunogenicity of the simultaneous administration of virosome hepatitis A and yellow fever vaccines.

BACKGROUND: The purpose of this study was to evaluate the tolerance and immunogenicity of a hepatitis A vaccine using immunopotentiating reconstituted influenza virosomes (IRIV) as adjuvant when administered simultaneously with a yellow fever vaccine (YFV). METHOD: An open prospective trial with two parallel groups was conducted with 105 volunteers to study the effect of these vaccinations on the anti-hepatitis A virus (HAV) antibody response. Half of the volunteers (53) received one dose of IRIV-HAV vaccine (Epaxal) and one dose of live attenuated YFV (Stamaril) on the same day at two different sites. Fifty-six volunteers were given a single injection of IRIV-HAV as a control group. Anti-HAV titers were measured at days 14, 28, months 3, 12, 13, and 24 using a standardized test (Enzymun test Anti-HAV). Neutralizing yellow fever antibodies were measured at days 14 and 28 for the YFV recipients. Regarding vaccine tolerance, the volunteers were asked to record all their adverse reactions on a standard report sheet for the 6 days following the immunization. RESULTS: Seroconversion rates for HAV were 88% after 14 days and 100% after 4 weeks. There was no statistically significant difference between the two groups every time the titers were checked (IRIV-HAV vs HAV only: D14: 81 vs 101; D28: 275 vs 368; M3: 153 vs 169; M12: 117 vs 226; geometrical mean titers (GMT) in mIU/mL). However, lower titers were found among male volunteers, and were not attributable to YFV administration. The seroconversion rates for YFV were 90% after 14 days and 96% after 4 weeks. No serious general side-effects and only mild local reactions were reported. The administration of a booster of IRIV-HAV at 12 months resulted in a 24-fold increase in GMT. CONCLUSION: When needed, the simultaneous administration of the IRIV-HAV and YFV is immunogenic, safe and well-tolerated, as volunteers seroconverted to both antigens, with no cross-interference.

[Unauthorized vaccines put on the market are useful for certain travelers]. / Les vaccins sans autorisation de mise sur le marché utiles à certains voyageurs.

Certain vaccines such as the amaril vaccine are highly recommended and even required from the traveller. Other vaccinations concern persons travelling in regions where they might be infected by pathogens not present in their countries of origin. There exist vaccines which are available in certain countries but which are not (or not yet) allowed on the French market. This is the case for the Japanese encephalitis (JE) and for the tick encephalitis (TE) of Central Europe. Details should be given about how the traveller can benefit from these vaccines, and about practical procedures to obtain them. The agents responsible are viruses transmitted by arthropods (the mosquito and the tick, respectively). The variability of the risk and the seasons of transmission, variable from one region to another (especially as far as JE is concerned), have to be taken into account. Also, the small risk of infection presently encountered and the small percentage of persons developing clinical syndromes after an infectious bite should be taken into consideration. Practically speaking, vaccination against the Japanese encephalitis is recommended to those persons who plan to stay in an endemic or epidemic region for several weeks during the season of transmission, especially if a trip into rural areas is entailed. As far as tick encephalitis is concerned, infection can take place in all rural areas (meadows, clearings, underwoods ...) of the Vosges and the zones east of them, especially in Central Europe, Russia and Siberia. While the decision is still justifiably pending as to whether to allow these vaccines on the market, it is possible to obtain from the public health administration a temporary authorization for their administration. Travellers should in any case be strongly advised to protect themselves against the bites of arthropods.

Populations of persons who must be vaccinated with priority.

During a major pandemic of influenza, it would be impossible to vaccinate the entire population. Thus, it is necessary to determine which groups of individuals must be immunized with priority, considering the additional constraints related to the actual situation: to seek to reduce transmission of the virus and to maintain the activity of the community, especially those involved in public services. Another unavoidable factor must also be taken into consideration: the capacity for manufacturing and distributing the vaccine on an emergency basis. Lastly, contingency and planning measures must be made to avoid having to improvise.

[A case of polyradiculoneuritis associated with dengue in a patient native to French Guiana]. / Un cas de polyradiculonévrite associé à une dengue chez une patiente originaire de la Guyane Française.

An acute polyradiculoneuritis in a woman native of French Guiana has been observed with serologic conversion against flaviviruses by inhibition of hemagglutination test. Dengue's diagnostic was been kept in spite of lack of causal virus isolation and non-typical clinical symptoms. Association dengue-polyradiculoneuritis appears quite uncommon and is worthy of note, in view of frequency of infection by Flaviviruses.

[Imported dengue in france (1989-1993). Conditions to be met for assuring an accurate etiological diagnosis]. / La dengue d'importation en France (1989-1993). Conditions à réaliser pour assurer un diagnostic étiologique fiable.

Every year, many travellers are going in endemic zone of dengue for more or less long stay. Back home, they show sometimes a feverish and algic syndrome reminding the dengue, and the confirmation of the diagnosis is required at the laboratory. In most cases, the impossibility to proceed to the isolation of the virus, the relative lack of specificity and the cross-reactions, that the available serological techniques do not allow to avoid, make delicate even impossible the interpretation of the results. A five-year assessment has nevertheless been attempted: it allows to establish that probably about several tens of dengue cases are imported each year in France. The conditions allowing to confirm biologically the clinical diagnosis are recalled and strict interpretation criteria are proposed.

[Current situation of yellow fever in Latin America]. / Situation actuelle de la fièvre jaune en Amérique latine.

Yellow fever endemicity is currently stabilized in South America: an average of 115 cases has officially been notified each year since 25 years (between 12 and 304 annual cases). These figures are underevaluated but no epidemic has been observed since 1983. Only sporadic or limited grouped cases have been reported. All declared cases correspond to people who have been infected within sylvatic areas, mainly adult forestmen. Within the last years, the majority of cases have occurred in Peru and Bolivia; the other cases have been observed in Brazil, in Columbia, in Ecuador and in French Guiana (imported strains from Surinam). This apparently low virus circulation may be due to massive campaigns of vaccination and to mosquito vector control. But this situation could suddenly reverse as observed in the past with yellow fever and the spring of the urban Aedes aegypti vector. Genetic and immunochemical heterogeneity has been demonstrated between South American and African yellow fever strains, which may reveal evolutionary divergence due to different ecological environment between the two continents. Yellow fever definitely remains a topical disease which requires a constant surveillance.

[Application of the polymerase chain reaction (PCR) to diagnosis in virology]. / Application de l'amplification génomique en chaine (PCR) au diagnostic en virologie.

Recall of the principle of the PCR and of its advantages: rapidity, possible automatization, high sensitivity allowing the detection of minute amounts of infectious agents, specificity depending on that of the primers used for the detection of the amplified product. But this technic has to be used with care to avoid any contamination which might give false positive results and requires controls. This procedure would allow to analyze the evolution and the variability of infectious agents by their sequence determination, thus providing a powerful tool for molecular epidemiology investigations. This method has already been used in many diagnoses of viral infections. The authors show results obtained on dengue viruses: 24 out of 32 sera were found positive (75%) by PCR whereas only 15 (47%) were positive by cell culture. On the other hand, 7 strains of dengue 2 virus of various regions throughout the world and isolated between 1969 and 1982 showed extensive degrees of variability.

[Rotavirus infections and their prevention with vaccines in children]. / Les infections a rotavirus et leur prévention vaccinale chez l'enfant.

Human rotaviruses are the most common cause of severe diarrhoea in children under two years in developing countries: the need of an effective rotavirus vaccine, safe, easy to administer and compatible with existing immunization schedules is now well-established. Molecular structure of rotaviruses (fragmented genome) and their antigenic variability (four human serotypes without cross-reactivity) explain some difficulties in vaccinal strategy. Furthermore, specific efficacy is not clearly evaluable because many others pathogens are responsible of diarrhoea. Immunological response is influenced by serological status before immunization, antigenicity of vaccinal strains, age of immunization. For all these reasons, some contradictory results are emerging from published field trials. Present candidate rotavirus vaccines are live vaccines, with oral administration of bovine or simian rotaviruses; recombinant and polyvalent strains were constructed and were under evaluation; a better strategy for dose administration, target population and interference with other live vaccines is in progress.

Proposals on the control of VERO cells used to prepare inactivated poliomyelitis vaccine.

The purpose of this study is to know if it is possible to prepare inactivated poliomyelitis vaccines on Vero cell culture. In the cloned cell line used to prepare the vaccines, we have looked for an eventual toxic effect by different system tests. The cells between the 148e and 151e passage used to prepare the vaccines were inoculated into: - suckling mice, rabbits and guinea pigs - embryonated eggs. The supernatant fluid of the cells was inoculated into: - Vero cells - Primary rabbit kidney cells - Primary monkey kidney cells. We have also looked for an eventual tumorigenic effect on immunodepressed mice with an antithymocytic serum. The results of the assays are presented and discussed.

[Several yellow fever cases in an endemic area in Ivory Coast: serological and epidemiological evidence (author's transl)]. / Diagnostic de plusieurs cas de fièvre jaune en zone d'émergence endémique en Côte-d'Ivoire.

1 - More than hundred febrile haemorrhagic jaundice cases with an unexpectedly high number of death happened in the north-west of the Ivory Coast between October 1977 and December 1977. It was the end of the rainy season and in this area, yellow fever is a dreadful eventuality. 2 - Epidemiological and serological survey was immediately carried out. Presence of numerous yellow fever potential vectors was well known and has been noticed in September 1977; there were some left in December 1977. Therefore no virus was isolated either in September or further. 3 - Haemagglutination-inhibition, complement-fixation and neutralization tests were performed with six flavivirus antigens, i.e. yellow fever, Wesselsbron, West Nile, Ntaya, Uganda S and Zika. 2 or 3 sera from 29 patients and 49 school children who have recent jaundice history, sometimes with haemorrhagic symptoms, were available. Single sera from 52 young rural workers and 402 inhabitants of surrounding villages were examined too. 4 - By the way of clinical, epidemiological, serological evidence, authors concluded 21 cases were certainly yellow fever. Evidence of 2 other cases was demonstrated by specific micropathological features. Furthermore, by serological results, 20 were probably yellow fever, 15 were inconclusive and 476 certainly not. 5 - Authors discussed some specific difficulties of yellow fever retrospective diagnosis in flavivirus endemic area.

[A strain of amaril virus isolated from Aedes africanus in the Ivory Coast]. / Une souche de virus amaril isolée d'Aedes africanus en Côte-d'Ivoire

The yellow fever virus has been isolated from a pool of Aedes africanus caught on men in a region situated between forest and savannah near Touba, in the Ivory Coast. This isolation, occurring at an interepidemic period, proves for the first time in West Africa, the part played by this mosquito in the transmission of the yellow fever virus.