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Describes use of the Okapi system, an experimental text retrieval system at City University, London, on TREC (Text Retrieval Conference) test collections to investigate probabilistic models and weighting functions; automatic ad hoc experiments; and routing and filtering for query optimization. Discusses interactive system evaluation. (LRW)

A comprehensive account of a probabilistic model of retrieval with new systematic experiments on TREC (Text Retrieval Conferences) Program material. Part 2 covers the further development of the model, with testing, and briefly considers other environment conditions and tasks, model training, concluding with comparisons with other approaches and an overall assessment. Key results are summarized. Data and results tables for both parts are given in Part 1. (Contains 64 references.) (AEF)

This two-part article combines a comprehensive account of a probabilistic model of retrieval with new systematic experiments on TREC (Text Retrieval Conferences) Program material. Part 1 covers the foundations and the model development for document collection and relevance data, along with the test apparatus. Data and results tables for both parts are given in Part 1. Key results are summarized in Part 2. (Contains 33 references.) (AEF)

Describes the Okapi projects and the work of the Centre for Interactive Systems Research at the City University of London (England). Okapi, an experimental text retrieval system, has been used as the basis for a series of projects addressing aspects of user information-seeking behavior and user-system interaction, as well as system design. (Author/LRW)

Discusses the use of text retrieval methods based on probabilistic models with Chinese language material, which are modeled on the Okapi information retrieval system. Topics include system architecture, test collections, weighting functions, and algorithms. (Author/LRW)

Summarizes the development of information retrieval evaluation ideas, describes the design of the TREC (Text Retrieval Conference) experiments, and discusses the Okapi team's participation in TREC. Highlights include the Cranfield projects that tested the principles of information retrieval system design, test collections, weighting functions, term selection for query expansion, and manual and interactive experiments. (Author/LRW)

The increasing complexity of evaluating information retrieval (IR) systems is discussed in terms of contributing factors and research methods. Examples are provided from experiments with weighted searching on a front-end system, information-seeking behavior and online catalogs, and the OKAPI experimental retrieval system. (21 references) (LAE)

Discusses term weighting formulae and their use for selecting new terms to enhance a search statement and for weighting the terms for retrieval purposes once selected. The Swets model of information retrieval system performance is described, an approach to term selection is presented, and future research is suggested. (five references) (LRW)

Discusses the problem of determining an adequate sample size for an information retrieval experiment comparing two systems on separate samples of requests. The application of statistical methods to information retrieval experiments is discussed, the Mann-Whitney U Test is used for determining minimum sample sizes, and variables and distributions are considered. (14 references) (LRW)

A Bayesian argument is used to suggest modifications to the Robertson and Jones relevance weighting formula to accommodate the addition to the query of terms taken from the relevant documents identified during the search. (Author)

Presents adaptation of a probabilistic theoretical model previously used in relevance feedback for use in automatic indexing of documents (in the sense of imitating) human indexers. Methods for model application are proposed, independence assumptions used in the model are interpreted, and the probability of a dependence model is discussed. (Author/MBR)

Purpose - An issue that tends to be ignored in information retrieval is the issue of updating inverted files. This is largely because inverted files were devised to provide fast query service, and much work has been done with the emphasis strongly on queries. This paper aims to study the effect of using parallel methods for the update of inverted files in order to reduce costs, by looking at two types of partitioning for inverted files: document identifier and term identifier. Design/methodology/approach - Raw update service and update with query service are studied with these partitioning schemes using an incremental update strategy. The paper uses standard measures used in parallel computing such as speedup to examine the computing results and also the costs of reorganising indexes while servicing transactions. Findings - Empirical results show that for both transaction processing and index reorganisation the document identifier method is superior. However, there is evidence that the term identifier partitioning method could be useful in a concurrent transaction processing context. Practical implications - There is an increasing need to service updates, which is now becoming a requirement of inverted files (for dynamic collections such as the web), demonstrating that a shift in requirements of inverted file maintenance is needed from the past. Originality/value - The paper is of value to database administrators who manage large-scale and dynamic text collections, and who need to use parallel computing to implement their text retrieval services. [ABSTRACT FROM AUTHOR]

Purpose - The generation of inverted indexes is one of the most computationally intensive activities for information retrieval systems: indexing large multi-gigabyte text databases can take many hours or even days to complete. We examine the generation of partitioned inverted files in order to speed up the process of indexing. Two types of index partitions are investigated: Termld and Dodd. Design/methodology/approach - We use standard measures used in parallel computing such as speedup and efficiency to examine the computing results and also the space costs of our trial indexing experiments. Findings - The results from runs on both partitioning methods are compared and contrasted, concluding that Dodd is the more efficient method. Practical implications - The practical implications are that the Dodd partitioning method would in most circumstances be used for distributing inverted file data in a parallel computer, particularly if indexing speed is the primary consideration. Originality/value - The paper is of value to database administrators who manage large-scale text collections, and who need to use parallel computing to implement their text retrieval services. [ABSTRACT FROM AUTHOR]

We have performed an F2 genetic screen to identify lethal mutations that map to the 44D-45B region of the Drosophila melanogaster genome. By screening 8500 mutagenized chromosomes for lethality over Df(2R)Np3, a deficiency which encompasses nearly 1% of the D. melanogaster euchromatic genome, we recovered 125 lines with lethal mutations that represent 38 complementation groups. The lethal mutations have been mapped to deficiencies that span the 44D-45B region, producing an approximate map position for each complementation group. Lethal mutations were analyzed to determine the phase of development at which lethality occurred. In addition, we have linked some of the complementation groups to P element-induced lethals that map to 44D-45B, thus possibly providing new alleles of a previously tagged gene. Some of the complementation groups represent potentially novel alleles of previously identified genes that map to the region. Several genes have been mapped by molecular means to the 44D-45B region, but do not have any reported mutant alleles. This screen may have uncovered mutant alleles of these genes. The results of complementation tests with previously identified genes in 44D-45B suggests that over half of the complementation groups identified in this screen may be novel. [ABSTRACT FROM AUTHOR]

Since the 1980s, yellow fever has reemerged across Africa and in South America. The total of 18 735 yellow fever cases and 4522 deaths reported from 1987 to 1991 represents the greatest amount of yellow fever activity reported to the World Health Organization (WHO) for any 5-year period since 1948. There is an excellent vaccine against yellow fever. At present, a high proportion of travelers to at-risk areas are reported to be immunized, reflecting widespread knowledge about the International Health Regulations. In South America, yellow fever remains an occupational hazard for forest workers, who should be immunized. However, Aedes aegypti mosquitoes are now present in urban areas in the Americas (including southern parts of the United States), and there is concern that yellow fever could erupt in explosive outbreaks. In Africa, a large proportion of cases have occurred in children. The WHO, the United Nations Children's Fund (UNICEF), and the World Bank have recommended that 33 African countries at risk for yellow fever add the vaccine to the routine Expanded Programme on Immunization; studies show that this would be highly cost-effective. To date, financing yellow fever vaccine has been a major problem for these countries, which are among the poorest in the world. For this reason, WHO has launched an appeal to raise $70 million for yellow fever control in Africa. [ABSTRACT FROM AUTHOR]

This paper examines statistical techniques for exploiting relevance information to weight search terms. These techniques are presented as a natural extension of weighting methods using information about the distribution of index terms in documents in general. A series of relevance weighting functions is derived and is justified by theoretical considerations. In particular, it is shown that specific weighted search methods are implied by a general probabilistic theory of retrieval. Different applications of relevance weighting are illustrated by experimental results for test collections. [ABSTRACT FROM AUTHOR]

We have established in vitro assays that allow the examination of co-stimulatory function of rheumatoid arthritis (RA) antigen-presenting cells (APC). Synovial fluid (SF) and peripheral blood (PB) APC co-stimulatory ability was compared in the activation of peptide-specific human T-cell clones. T-cell receptor (TCR) stimulation by peptide or anti-CD3 antibody allowed the direct comparison of SF and PB APC co-stimulatory activity, separately from their ability to process antigen. SF APC from 15 RA patients consistently enhanced T-cell proliferation when compared to their PB counterparts. Moreover, increasing the numbers of PB APC present resulted in only a minor increase in T-cell proliferation, failing to achieve levels stimulated by SF APC. We propose that the enhanced co-stimulatory function of synovial APC may be a significant factor in the persistence of local immune responses in RA. [ABSTRACT FROM PUBLISHER]

Presents a letter to the editor commenting on researcher W.S. Cooper's two-part paper, "On Selecting a Measure of Retrieval Performance," published in an issue of the "Journal of the American Society for Information Science."

Objective: To estimate the cost-effectiveness of providing Haemophilus influenzae type b (Hib) vaccine to children in Moscow in routine immunization services., Methods: The incidence of Hib meningitis among children aged <5 years in Moscow was obtained from a prospective surveillance study undertaken during October 1999-September 2001, with treatment cost data collected for all cases. Sequelae in surviving children were assessed in December 2002. The costs of Hib vaccination in Moscow were estimated assuming a vaccine price of US dollar 5 per dose and the same four-dose schedule and 97% coverage as for diphtheria-tetanus-pertussis vaccine. The most uncertain variables were varied in a sensitivity analysis., Results: The annual incidence of Hib meningitis was 5.7 per 100,000 children <5 years. The average treatment cost for an acute Hib meningitis case was US dollar 1296. For a patient with sequelae, the average additional lifetime discounted treatment cost was US dollar 15,820. The total annual cost of Hib vaccination of infants in Moscow was estimated as US dollar 1.5 million per year. In the base case analysis, the cost-effectiveness ratios amount to US dollar 77,503 per Hib meningitis case averted and US dollar 10,842 per discounted disability adjusted life year averted. The break-even vaccine price, where the annual vaccination costs equal annual treatment costs averted, is only US dollar 0.04 per dose in the base case scenario. If discounted indirect costs are included, the break-even vaccine price is US dollar 0.5 per dose., Conclusion: In Moscow, the incidence of Hib meningitis is low and the costs of hospitalization and subsequent medical treatment are relatively inexpensive. Given these factors, Hib vaccine at US dollar 5 per dose would not be a cost-effective option in Moscow at the present time.

The WHO Vaccine Trial Registry prospectively registers clinical vaccine studies supported by WHO. Through December 1999, the registry includes 103 studies from 43 countries, with nearly 80% in developing countries. The registry documents an expanding research capacity, with an average of 3.9 new studies per year during 1987-1993, rising to 10.7 per year during 1994-2000. The studies concern a broad spectrum of infectious organisms, including: Clostridium tetani (tetanus), dengue virus, enterotoxigenic Escherichia coli (ETEC), Haemophilus influenzae type b (Hib), hepatitis B virus, measles virus, Mycobacterium tuberculosis, Neisseria meningitidis (meningococcus), poliovirus, respiratory syncytial virus (RSV), rotavirus, Salmonella typhi, Shigella, Streptococcus pneumoniae (pneumococcus), and Vibrio cholerae.

IL-2 responses are susceptible to suppression by TGFbeta, a cytokine widely implicated in suppression of inflammatory responses and secreted by many different tumor cell types. There have been conflicting reports regarding inhibition of IL-2-induced STAT3 and STAT5 phosphorylation by TGFbeta and subsequent suppression of immune responses. Using TGFbeta-producing multiple myeloma tumor cells we demonstrate that tumor-derived TGFbeta can block IL-2-induced proliferation and STAT3 and STAT5 phosphorylation in T cells. High affinity IL-2R expression was required for the suppression of IL-2 responses as a novel CD25(-) T cell line proliferated and phosphorylated STAT3 when cultured with tumor cells or rTGFbeta1. Activating T cells with IL-15, which does not use the high affinity IL-2R, completely restored the ability of T cells to phosphorylate STAT3 and STAT5 when cultured with tumor cells. IL-15-treated T cells proliferated normally when cocultured with tumor cells or rTGFbeta1, whereas IL-2 responses were consistently inhibited. Preincubation with IL-15 also restored the ability of T cells to respond to IL-2 by phosphorylating STAT3 and STAT5, and proliferating normally in the presence of tumor cells. IL-2 pretreatment did not restore T cell function. IL-15 also restored T cell responses by T cells from multiple myeloma patients, and against freshly isolated bone marrow tumor samples. Thus, activation of T cells by IL-15 renders T cells resistant to suppression by TGFbeta1-producing tumor cells and rTGFbeta1. This finding may be exploited in the design of new immunotherapy approaches that will rely on T cells avoiding tumor-induced suppression.

Background: The immunogenicity of oral poliovirus vaccine (OPV), particularly the type 3 component, is lower in infants in most developing countries than in infants in industrialized countries. We conducted a multicenter trial in Oman to evaluate the response to a supplemental dose of four poliovirus vaccine formulations., Methods: At nine months of age, infants were randomly assigned to receive inactivated-poliovirus vaccine (IPV), administered subcutaneously; trivalent OPV manufactured in the United States or in Europe; or monovalent type 3 OPV. Serum samples were collected at enrollment and 7 and 30 days later. All of the infants had previously received five doses of OPV., Results: We enrolled 1025 infants; 785 (76.6 percent) met all the study requirements. At enrollment, 96.8 percent of the infants were seropositive for poliovirus type 1, 98.0 percent for type 2, and 88.0 percent for type 3. At 30 days there were no significant increases in type 3 seroprevalence or in the median antibody titer in the groups of infants who received OPV. Among the recipients of IPV, type 3 seroprevalence increased from 87.8 percent at enrollment to 97.1 percent at 30 days (P<0.001), and the median antibody titer increased from 1:228 to 1:1448 or higher (P<0.001). The rapid initial increase in the antibody titer suggests a secondary immune response., Conclusions: A supplemental dose of IPV has excellent immunogenicity and leads to increases in the titer of antibodies against type 3 poliovirus, whereas supplemental doses of the oral vaccines do not have these effects.

The germ cell precursors of Drosophila (pole cells) are specified by maternally supplied germ plasm localized to the posterior pole of the egg. One component of the germ plasm, germ cell-less (gcl) mRNA, encodes a novel protein which specifically localizes to the nuclear envelope of the pole cell nuclei. In addition to its maternal expression, gcl is zygotically expressed through embryonic development. In this report, we have characterized a null allele of germ cell-less to determine its absolute requirement during development. We have found that gcl activity is required only for the establishment of the germ cell lineage. Most embryos lacking maternal gcl activity fail to establish a germline. No other developmental defects were detected. Examination of germline development in these mutant embryos revealed that gcl activity is required for proper pole bud formation, pole cell formation, and pole cell survival. Using this null mutant we have also assayed the activity of forms of Gcl protein with altered subcellular distribution and found that localization to the nuclear envelope is crucial for promoting pole cell formation, but not necessary to initiate and form proper pole buds. These results indicate that gcl acts in at least two different ways during the establishment of the germ cell lineage., (Copyright 1999 Academic Press.)

Mumps is an acute infectious disease caused by a paramyxovirus. Although the disease is usually mild, up to 10% of patients can develop aseptic meningitis; a less common but more serious complication is encephalitis, which can result in death or disability. Permanent deafness, orchitis, and pancreatitis are other untoward effects of mumps. Based on data reported to WHO up to April 1998, mumps vaccine is routinely used by national immunization programmes in 82 countries/areas: 23 (92%) of 25 developed countries, 19 (86%) of 22 countries with economies in transition (mainly the Newly Independent States of the former Soviet Union), and 40 (24%) of 168 developing countries. Countries that have achieved high coverage have shown a rapid decline in mumps morbidity. Furthermore, in many of these countries, mumps-associated encephalitis and deafness have nearly vanished. This review considers the disease burden due to mumps; summarizes studies on the immunogenicity, efficacy, and safety of different strains of mumps vaccine; and highlights lessons learned about implementing mumps immunization in different countries. Countries already using mumps vaccine should monitor immunization coverage and establish routine mumps surveillance with investigation of outbreaks. Where mumps is targeted for elimination, countries need to add a second dose of mumps vaccine for children, keeping in mind that the disease may still occur in susceptible adults.

Effective attenuated live virus mumps vaccines have been available for more than 30 years. Vaccine strains have been developed on various cell culture systems; the attenuated mumps virus strain most commonly used is the Jeryl Lynn strain. Various vaccines differ in their immunogenicity, efficacy and associated adverse events. It is estimated that the immunization coverage needed to block the transmission of mumps virus is at least 70%. Models indicate that low to moderate levels of mumps vaccine coverage may actually increase the number of susceptibles and the number of cases in older age groups. Benefit-cost analyses in a number of countries have found that the introduction of mumps vaccine is economically justifiable, as vaccination can avert the considerable medical and economic costs associated with mumps morbidity. Countries that do not immunize against mumps continue to register high mumps morbidity, and pay a high toll from neurological and other complications of mumps. Poland, which already has a high level of measles vaccine coverage, should make efforts to replace monovalent measles vaccine with trivalent measles-mumps-rubella (MMR) vaccine.

Mumps is commonly considered a "mild" infectious disease in children because death due to mumps is very rare. However, mumps causes a high rate of complications in young adults, and its burden should not be underestimated. Before the introduction of vaccine, mumps was a common infectious disease with high incidence rates which exceeded 100 per 100,000 population in most countries. Poland continues to belong to the group of countries, which do not use mumps vaccine. In Poland, the number of reported mumps cases per year ranges from 40,000 to 220,000, yielding an annual incidence rates of 110 and 570 per 100,000 population. It is estimated that each year in Poland, mumps causes 1000 cases of aseptic meningitis (range 400 to 2,200), 100 cases of encephalitis, 250 to 1375 cases of epidymo-orchitis in post-pubertal men, 50-275 cases of oophoritis in women. The age distribution of mumps cases is characteristic for a country that does not use mumps vaccine. For more that 20 years, the highest mumps incidence has occurred in children aged 5-9 years. In many countries the number of reported cases has declined significantly following the introduction of mumps vaccine, and in several countries the incidence has fallen to less than 1 per 100,000 population. Several countries using mumps vaccine have reported a shift in the age distribution of mumps cases, with an increased incidence in older children and young adults. Countries with high levels of coverage with measles-mumps-rubella (MMR) vaccine have nearly eliminated encephalitis associated with these diseases. A few countries using mumps vaccine have experienced relative resurgence of the disease, either due to incomplete vaccine coverage of certain age groups (USA) or problems with the long-term immunogenicity of mumps vaccine based on the Rubini strain (Portugal, Switzerland).

The production of proinflammatory cytokines can be regulated by several factors that exert activating or inhibitory effects. IL-4, IL-10, IL-13, TGF-beta, and PGE2 have demonstrated a very wide range of potent macrophage-deactivating activities and, specifically, down-regulation of the production of many proinflammatory monokines. IL-12 plays a key role during immune response by providing a link between natural resistance and adaptive immunity. We and others have previously shown an impairment in IL-12 production by PBMC from HIV-1-infected individuals in response to various stimuli, but defining the mechanism responsible remains elusive. In this study, we observed that pretreatment of PBMC from patients with IL-4 or IL-13 for 24 h primes the cells for enhanced production of IL-12 in response to Staphylococcus aureus, and almost completely restores their deficient IL-12 production when compared with healthy controls. Although this priming effect was completely abrogated by IL-10 and PGE2, IL-10 was produced equivalently by untreated and IL-4- or IL-13-pretreated PBMC from both patients and controls. Additionally, indomethacin, which shuts off PGE2 synthesis, and cAMP-blocking reagents failed to restore or enhance IL-12 production. The priming effect of IL-4 and IL-13 is at the transcription level for both p40 and p35 genes. This complete restoration of IL-12 production by Th2-associated cytokines was unexpected in light of the mutually antagonistic roles of IL-12 and IL-4 in promoting Th1 or Th2 immune responses.

We have embarked on a molecular cloning approach to the investigation of sex determination in Silene latifolia Poiret, a dioecious plant species with morphologically distinguishable sex chromosomes. One of our key objectives was to define a range of genes that are up-regulated in male plants in response to Y chromosome sex-determination genes. Here we present the characterization of eight male-specific cDNA sequences and classify these according to their expression dynamics to provide a range of molecular markers for dioecious male flower development. Genetically female S. latifolia plants undergo a partial sex reversal in response to infection by the parasitic smut fungus Ustilago violacea. This phenomenon has been exploited in these studies; male-specific cDNAs have been further categorized as inducible or noninducible in female plants by smut fungus infection. Analysis of the organ-specific expression of male-specific probes in male and female flowers has also identified a gene that is regulated in a sex-specific manner in nonreproductive floral tissues common to both male and female plants. This observation provides, to our knowledge, the first molecular marker for dominant effect of the Y chromosome in nonreproductive floral organs.

Sex determination in Silene latifolia is controlled by heteromorphic sex chromosomes. Female flowers have five fused carpels and ten arrested stamen primordia. The male-determining Y chromosome overrides female development to suppress carpel formation and promote stamen development. The isolation and characterization of two S. latifolia. Male enhanced cDNAs, Men-9a and Men-9b, which probably represent different alleles of a novel gene are reported here. Men-9a and Men-9b share 91.8% coding sequence nucleotide identity, yet only 85.4% amino acid identity. The Men-9 cDNAs are related to the previously reported MROS3 cDNA from S. latifolia. However, MROS3 is not present in the S. latifolia population used in these studies and the expression dynamics of Men-9a and Men-9b contrast dramatically with those reported for MROS3. Men-9 cDNAs are expressed primarily in anthers of young male flowers, with highest expression in 1-2 mm buds. Men-9 expression is also observed at a low level in female flowers. In situ hybridization analysis reveals two phases of Men-9 expression. The first phase is during a common stage of early stamen development in male and female flowers prior to stamen arrest in female flowers. The second phase of Men-9 expression is maximal in the epidermis and endothecium of Y chromosome- and Ustilago violacea-induced stamens; expression in male and female flowers extends to the epidermis of the staminal nectaries with strict boundaries at the second and fourth whorls, Men-9 gene expression therefore delineates the boundaries of the third floral whorl in S. latifolia flowers.

Seroprevalence and geometric mean titers (GMTs) were compared at 6 and 10 months after vaccination with monovalent type 1 oral poliovirus vaccine (OPV) at 6 months and trivalent OPV at 7 and 9 months. Group 1 had received 4 doses of OPV, group 2 OPV at birth and 3 doses of OPV and inactivated poliovirus vaccine (IPV), and group 3 placebo at birth and 3 doses of IPV. A total of 547 infants completed the study. At 10 months, seroprevalence to poliovirus type 1 was 98%, 99%, and 98% in groups 1, 2, and 3; 100%, 100%, and 98% to poliovirus type 2; and 80%, 96%, and 91% to poliovirus type 3. Differences in seroprevalence among the groups were significant for poliovirus type 3 (P < .001). Between 6 and 10 months, significant increases in seroprevalence and GMTs occurred for poliovirus type 1 but not for types 2 and 3. Two OPV doses following 3 IPV doses did not significantly increase seroprevalence or raise GMTs for poliovirus types 2 and 3; however, significant increases were found for poliovirus type 1, which may have benefitted from monovalent type 1 administration.

In 1995, the WHO Global Programme for Vaccines and Immunization established a Vaccine Trial Registry. As of September 1996, this registry included 50 WHO-supported vaccine trials, of which 25 (50%) were completed studies. The vaccines most frequently tested have been against measles (9 trials), poliovirus (8 trials), cholera (8 trials), enterotoxigenic Escherichia coli (4 trials), and pneumococcus (4 trials). Nearly 80% of these trials have been conducted in developing countries, with the largest number being in Africa. Among the 25 completed trials, outcomes measured were immune response (24 trials), adverse reactions (13 trials), morbidity (4 trials), and mortality (1 trial). WHO's contributions to these studies include direct funding, assistance with study design, site visits, data analysis, vaccine procurement, and vaccine potency testing.

Since the mid-1980s, there has been growing interest in adapting the lot quality (LQ) technique to monitor the quality of health care services, especially in developing countries. This global review has identified a total of 34 LQ surveys conducted from 1984 to 1996 in Africa, the Americas, Europe, South-East Asia, and the Western Pacific. Health care parameters assessed in the surveys varied and some surveys assessed more than 1 health parameter: 24 surveys assessed immunization coverage, 9 examined women's health issues such as family planning and antenatal care, 5 assessed use of oral rehydration therapy, 5 estimated disease incidence, and 3 others evaluated health worker performance. These studies indicate that LQ is a practical, relatively low-cost field method which is increasingly being applied in health programmes.

In 1995-96 we conducted a review of rubella immunization strategies. Worldwide, 78 countries (more than one-third) reported a national policy of using rubella vaccine. This was closely related to country economic status. Based on the United Nations country classification, rubella vaccine is used in 92% of industrialized countries, 36% of those with economies-in-transition, and 28% of developing countries. Cases of congenital rubella syndrome (CRS) may be prevented as follows: by providing direct protection to women and/or schoolgirls (a selective vaccination strategy); by vaccinating boys and girls to provide indirect protection by reducing the transmission of rubella virus (a childhood vaccination strategy); or by a combination of these approaches (a combined strategy). A combined strategy was most commonly reported (60% of countries); seven countries (9%) reported a selective strategy; and 24 countries (31%) reported only childhood immunization. Experience has shown that it is essential to include vaccination of women of childbearing age in any rubella control strategy. Childhood vaccination alone may pose a risk of an increase in CRS cases. Although many countries have introduced rubella vaccine, few report any data on the impact of vaccination. Countries using rubella vaccine need to establish surveillance for rubella and CRS and monitor coverage in each of the target groups.

Congenital rubella syndrome (CRS) can lead to deafness, heart disease, and cataracts, and a variety of other permanent manifestations. In developing countries, the burden of CRS has been assessed as follows: by surveillance of CRS; by surveillance of acquired rubella; by age-stratified serosurveys; and by serosurveys documenting the rubella susceptibility of women of childbearing age. During rubella outbreaks, rates of CRS per 1000 live births were at least 1.7 in Israel, 1.7 in Jamaica, 0.7 in Oman, 2.2 in Panama, 1.5 in Singapore, 0.9 in Sri Lanka, and 0.6 in Trinidad and Tobago. These rates are similar to those reported from industrialized countries during the pre-vaccine era. Special studies of CRS have been reported from all WHO regions. Rubella surveillance data show that epidemics occur every 4-7 years, similar to the situation in Europe during the pre-vaccination era. In developing countries, the estimated average age at infection varies from 2-3 years to 8 years. For 45 developing countries we identified serosurveys of women of childbearing age that had enrolled > or = 100 individuals. The proportion of women who remained susceptible to rubella (e.g. seronegative) was < 10% in 13 countries. 10-24% in 20 countries, and > or = 25% in 12 countries. Discussed are methods to improve the surveillance of rubella and CRS in developing countries.

Pertussis is a serious disease for children in all countries, but it is more severe in the developing world. Disease incidence, complication rates and case fatality rates are highest in infants: unimmunized and incompletely immunized young children are also at risk in adults, pertussis is usually mild or asymptomatic, but older individuals may serve as reservoirs for transmission. Some 70 million cases of pertussis were prevented in 1994 due to immunization with the current whole cell vaccine. WHO emphasizes the importance of early completion of the primary series of vaccinations, with three doses of diphtheria-tetanus-pertussis (DTP) vaccine one month apart starting at six weeks of age. For the past five years, nearly 80% of infants worldwide have received three DTP doses by their first birthday. Despite this, an estimated 40 million cases of pertussis occurred in 1994, indicating the need to increase coverage. The challenge is to reach 90% coverage of infants in all countries by the year 2000 but this will require further efforts to improve immunization programmes.

A massive diphtheria epidemic in Eastern Europe has resulted in increased anxiety that this disease could spread to other countries. This fear is realistic because there is a gap in the diphtheria immunity in large segments of the adult population in many industrialized countries. Experience to date suggests that an immunity gap in adults coupled with the presence of large numbers of susceptible children and adolescents creates the potential for an extensive epidemic. To prevent epidemics, countries should consider the immunogenicity and duration of protection provided by diphtheria toxoid given to children in the primary series and as booster doses. This paper reviews general issues related to the formulation of diphtheria immunization strategies, especially the need for booster doses in adults and the rationale for use of lower-strength diphtheria toxoid for persons older than 6 years of age.

Seroresponses to trivalent oral poliovirus vaccine are not uniform throughout the world. Definition of the variables that determine successful immunization is vital to ensure global polio eradication. One such variable may be dosage interval. To investigate this effect 108 infants were enrolled in a clinical trial and randomly assigned to receive three doses of trivalent oral poliovirus vaccine (standard United States formulation) at 2, 3 and 4 or 2, 4 and 6 months of age. After three doses of vaccine given before 6 months of age, immunity was virtually complete for each of the three poliovirus types in both groups. After two doses the seroresponse rate to each type was less with the shorter dose interval. However the difference was not significant (P = 0.15) in the sample size studied. Such responses differ markedly from those seen in developing countries, where four or more doses of vaccine may fail to provide complete protection. Differences other than dosage interval must contribute to those failures.

Following the introduction of routine immunization with diphtheria toxoid in the 1940s and 1950s, diphtheria incidence declined dramatically in countries of the industrialized world. At the beginning of the 1980s many of these countries were progressing toward elimination of the disease. However, since the mid-1980s there has been a striking resurgence of diphtheria in several countries of Eastern Europe. For 1993, WHO received reports of 15,211 diphtheria cases in Russia and 2,987 cases in Ukraine. The main reasons for the return of diphtheria in these countries were: decreasing immunization coverage among infants and children waning immunity to diphtheria in adults, movements of the population during the last few years, and an irregular supply of vaccines. The outbreak spread to neighboring countries and in 1993 cases were reported in Azerbaijan, Belarus, Estonia, Finland, Kazakhstan, Latvia, Lithuania, Poland, Tajikistan, Turkey, and Uzbekistan. Epidemiological patterns of diphtheria are changing in developing countries, and the disease seems to be following patterns seen in industrialized countries 30 to 40 years ago. In developing countries, routine immunization against diphtheria was introduced in the late 1970s with the Expanded Programme on Immunization. In these countries, coverage of infants with 3 doses of diphtheria toxoid reached 46% in 1985, and 79% in 1992. Recent diphtheria outbreaks in Algeria, China, Ecuator, Jordan, Lesotho and Sudan demonstrate a shift in the age distribution of cases to older children and adults. Rapid clinical and public health responses are required to control diphtheria outbreaks. Three major measures are indicated: high immunization coverage of target groups, prompt diagnosis and management of diphtheria cases, and rapid identification of close contacts with their effective management to prevent secondary cases.

In the past, diphtheria was considered one of the most serious childhood diseases because it took a heavy toll in health and life among preschool-aged children. Prior to the widespread availability of diphtheria toxoid, nearly 70% of cases were in children younger than 15 years of age. In the industrialized countries, immunization against diphtheria became widespread in the 1940s and 1950s. This led to a marked decrease in the incidence of diphtheria. There was also a decrease in circulating toxigenic Corynebacterium diphtheriae organisms, resulting in less natural boosting of antibody levels. This had led to gaps in the immunity of the adult population. Since 1990, diphtheria has made a spectacular comeback in several European countries, with a high proportion of cases in adults. In developing countries, immunization of infants with diphtheria toxoid was introduced with the Expanded Programme on Immunization in the late 1970s. Coverage rose slowly to 46% in 1985 and 79% in 1992. Because the pool of immunized persons is not yet large, the process of maintaining immunity still operates through natural mechanisms, including frequent skin infections caused by C. diphtheriae. But recently, several developing countries where coverage has been high for 5-10 years have reported diphtheria outbreaks. These outbreaks have been characterized by high case fatality rates, a large proportion of patients with complications, and their occurrence in both young and older age groups. In all countries, priority should be given to efforts to reach at least 90% coverage with three doses of diphtheria toxoid in children below one year of age. In countries where diphtheria has been successfully controlled, immunity levels should be maintained by booster doses.

Background: Our preliminary results showed that pentoxifylline improves survival after cecal ligation and puncture (CLP), even though in this model inhibition of tumor necrosis factor (TNF) activity decreases survival. In this study we tested the hypothesis that pentoxifylline improves survival after CLP, not by inhibiting TNF synthesis but by exerting its effect on leukocyte adhesiveness, neutrophil sequestration, recruitment of cells into the focus of sepsis, and interleukin-1 (IL-1) expression., Methods: Pentoxifylline, 10 or 100 mg/kg/day, was administered to mice after CLP by infusion for 3 days. The following was measured at 24 hours for the group with improved survival: (1) serum TNF by enzyme-linked immunosorbent assay, (2) TNF and IL-1 beta mRNAs in lung and peritoneal macrophages by the differential polymerase chain reaction, (3) lung myeloperoxidase by a colorimetric assay, (4) leukocyte CD11b/CD18 by flow cytometry, and (5) peritoneal exudate cells by manual counting., Results: Only the low-dose pentoxifylline increased survival. Pentoxifylline reduced IL-1 beta mRNA expression in lung and peritoneal macrophages but not TNF mRNA or immunoreactive TNF in the serum. The myeloperoxidase content of lung was reduced by pentoxifylline, but leukocyte CD11b/CD18 expression did not change. Pentoxifylline increased the number of cells in the peritoneum after CLP., Conclusions: Pentoxifylline improves survival after CLP without inhibiting TNF synthesis or expression of CD11b/CD18 on leukocytes. Pentoxifylline treatment reduced lung neutrophil sequestration and IL-1 beta mRNA levels and increased cell recruitment in the peritoneum.

In 1988 the World Health Assembly set the goal of global poliomyelitis eradication by the year 2000. Substantial progress has been made, and 143 countries reported no poliomyelitis cases associated with the wild virus in 1993. This article reviews the immunological considerations relevant to interrupting the transmission of wild polioviruses with vaccines. Although serum immunity prevents poliomyelitis in the individual, it is local immunity that is important in preventing the transmission of polioviruses in the community. Natural infection and vaccination with oral polioviruses vaccine (OPV) produce local immunity in the intestine and the nasopharynx in about 70-80% of individuals. In contrast, inactivated poliovirus vaccine (IPV) produces local intestinal immunity in only 20-30% of the individuals. With either vaccine, however, a substantial proportion of the immunized population can transmit the wild virus. Moreover, although serum immunity is long-lasting, limited data suggest that local immunity may not be as persistent. To interrupt the transmission of wild polioviruses efforts should be made to achieve and sustain high levels of poliovirus vaccine coverage. Recent outbreaks show that wild poliovirus poses a risk for unimmunized individuals, even when overall coverage levels are high. Delivery of poliovirus vaccine to hard-to-reach populations will be of increasing importance as countries progress toward the final stages of poliomyelitis eradication. The immunization status of persons from poliomyelitis-free countries should be updated prior to travel to poliomyelitis-endemic areas.