INCIDENCE of disease. Foreign reports; reports of cholera, plague, smallpox, typhus fever, and yellow fever received during the current week.
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Immunization of monkeys with yellow fever virus-specified nonstructural protein NS1 resulted in protection against fatal hepatitis as well as marked reduction in the magnitude of viremia after subcutaneous challenge with yellow fever virus. The results may be relevant to the design of possible subunit or recombinant flavivirus vaccines.
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A survey for yellow fever haemagglutination inhibiting antibody was carried out before and after the 1987 yellow fever epidemics in Nigeria in two localities in Oyo State, namely: Ibadan and Ogbomosho. A total of 129 sera were collected from the two localities before the epidemic. The overall prevalence of yellow fever HI antibody was 37%. A breakdown of positive sera showed that 30/100 and 18/29 sera tested in Ibadan and Ogbomosho respectively were positive. There was a higher prevalence of HI antibody in males (43%) than in females (32%). Of the 48 yellow fever positive sera 23(47%) contained HI antibody to West Nile and 26(52%) to Potiskum viruses. Following the epidemic and the subsequent mass vaccination campaign with the 17D yellow fever vaccine, 200 sera were randomly collected from the same localities. The overall prevalence of yellow fever HI antibody was 67%. The percentage of positive sera in the individual locality was 63% in Ibadan and 73% in Ogbomosho. No statistical difference was observed in the prevalence of yellow fever antibody in both sexes following the yellow fever vaccination campaign (P greater than 0.05). Tests on yellow fever HI antibody positive sera collected after the vaccination campaign showed that 74% and 82% were positive for West Nile and Potiskum HI antibody respectively. Results of this study showed that despite the massive antiyellow fever vaccination campaign there was still a high percentage of seronegative persons in the two communities.
Four recombinant vaccinia viruses were constructed for expression of different portions of the 17D yellow fever virus (YFV-17D) open reading frame. A recombinant, vP869, expressing prM and E induced high titers of neutralizing and hemagglutination inhibiting antibodies in mice and was protective against intracranial challenge with the French neurotropic strain of YFV. Levels of protection were equivalent to those achieved by immunization with the YFV-17D vaccine virus. Recombinant vaccinia viruses expressing E and NS1, C prM, E, NS1, or only NS1 failed to protect mice against challenge with YFV despite eliciting antibodies to NS1. The vP869-infected HeLa cells produced a particulate extracellular hemagglutinin (HA) similar to that produced by YFV-infected cells, supporting previous studies with Japanese encephalitis virus (Mason et al., 1991), suggesting that the ability of recombinant vaccinia virus to produce extracellular HA particles is important for effective flavivirus immunity.
Yellow fever vaccines are routinely assayed by plaque assay. However, the results of these assays are then converted into mouse LD(50) using correlations/conversion factors which, in many cases, were established many years ago. The minimum required potency in WHO Recommendations is 10(3) LD(50)/dose. Thirteen participants from 8 countries participated in a collaborative study whose aim was to assess the suitability of two candidate preparations to serve as an International Standard for yellow fever vaccine. In addition, the study investigated the relationship between the mouse LD(50) test and plaque forming units with a view to updating the WHO recommendations. Plaque assays were more reproducible than mouse assays, as expected. Differences in sensitivities of plaque assays were observed between laboratories but these differences appear to be consistent within a laboratory for all samples and the expression of potency relative to the candidate standard vaccine improved the reproducibility of assays between laboratories. However, the use of potencies had little effect on the between laboratory variability in mouse LD(50) assays. There appears to be a consistent relationship between overall mean LD(50) and plaques titre for all study preparations other than sample E. The slope of the correlation curve is >1 and it would appear that 10(3) LD(50) is approximately equivalent to 10(4) plaque forming units (PFU), based on the overall means of all laboratory results. The First International Standard for yellow fever vaccine, NIBSC Code 99/616, has been established as the First International Standard for yellow fever vaccine by the Expert Committee of Biological Standards of the World Health Organisation. The International Standard has been arbitrarily assigned a potency of 10(4.5) International Units (IU) per ampoule. Manufacturers and National Control Laboratories are including the First International Standard for yellow fever vaccine in routine assays so that the minimum potency in IU of vaccines released for use and which meet the current minimum potency of 10(3) LD(50) in mouse assays, can be determined. These data will be analysed before a review of the WHO requirements, including the minimum potency per dose, is undertaken.
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During the 1983 yellow fever epidemic in Burkina Faso, vaccinations were performed with a stabilized yellow fever 17D vaccine. Samples of vaccine were collected in different places during the vaccination campaigns. The virus titers of these samples were compared with those of vaccine samples of the same batches stored at--20 degree C in the Institut Pasteur in Dakar. There was no significant decrease of the titer when the vaccine had been stored in the conditions recommended by the expanded programme on immunization. The results confirm the experimental data on the stability of this vaccine. A serological survey carried out in young children showed that about 90% have hemagglutination inhibition antibodies following the vaccination.
Yellow fever virus has a special place in medical history as the first animal virus isolated and as the prototype virus in the genus Flavivirus, which contains many serious human pathogens. Only recently, its closely related viruses within the group were identified phylogenetically. In this study, we obtained complete or near complete genome sequences of two viruses most closely related to yellow fever virus: Sepik virus of Papua New Guinea and Entebbe bat virus of Africa. Based on full-genomic characterization and genomic traits among related viruses, we identified Sepik virus to be most closely related to yellow fever virus and analyzed the pattern of repeat and conserved sequence motifs in the 3'-noncoding region among the members of yellow fever virus cluster. We also discuss the geographic dispersal as a part of ecological traits of this lineage of flaviviruses.
Yellow fever, an acute mosquito-borne viral haemorrhagic fever, is preventable by use of the live, attenuated 17D vaccine. The vaccine is used principally in tropical climates and is subject to potentially adverse conditions. Lyophilized vaccine without stabilizers deteriorates rapidly when exposed to temperatures above -20 degrees C. In 1987, the WHO recommended that each lot of vaccine meet the following stability test: maintenance of potency (> 1,000 mouse i.c.LD50/human dose) with mean loss of titre < 1.0 log10 after being held at 37 degrees C for 14 days. In 1987, only 5 out of 12 yellow fever vaccines produced worldwide met the stability standards. To improve stability of the vaccine, a number of additives have been systematically investigated. A successful formulation, now used by a number of manufacturers, employs sugars, amino acids, and divalent cations [lactose (4%), sorbitol (2%), histidine (0.01 M), alanine (0.01 M), in phosphate buffered saline with Ca2+ and Mg2+]. As opposed to vaccine produced without stabilizers, which loses 1.5-2.5 log10/dose, stabilized vaccines lose only 0.3-0.5 log10 after being held at 37 degrees C for 14 days. The vaccine is stable after storage for > or = two years at 4 degrees C and 22 degrees C, and has a stability profile as good or better than many other live and inactivated vaccines currently used in the EPI, including measles, pertussis, oral and inactivated poliomyelitis vaccines. WHO is taking steps to enssure that all 11 current YF vaccine manufacturers produce vaccines that meet accepted stability standards. The principal rationale for increasing 17D vaccine stability beyond that achieved with the present stabilizers would be the improvement in stability of other EPI vaccines, to the point where yellow fever vaccine was the most sensitive vaccine among those deployed. The acceptable characteristics of current stabilized 17D vaccines and the high cost of changing and validating new vaccine formulations precludes a major investment at this time. Despite its stability when freeze dried, yellow fever 17D vaccine is quite unstable after reconstitution and must be discarded after one hour. Improvement in vaccine stability after reconstitution would thus reduce cost, stretch supplies of vaccine, and ensure against vaccine failures due to use of degraded vaccine. This is an area for future research.
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