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The replacement of water with deuterium oxide significantly improves the thermal stability of the oral poliovirus vaccine.

The poliomyelitis eradication programme relies largely on the massive administration of the oral poliovirus vaccine (OPV). The major difficulty in assuring good vaccine coverage, especially in hot climates, is the thermostability of the vaccine. Several attempts have been made to stabilize the OPV with limited benefits. In this report, we describe a heavy water based stabilization procedure, which has been shown to increase the thermostability of the vaccine, notably at temperatures which are commonly encountered during usual transportation in conditions of cold chain failure. Safety considerations regarding the human use of heavy water containing bioproducts are discussed.

Animals↗

Power cuts and EPI vaccine storage.

OBJECTIVE: To study the integrity of EPI vaccine storage during interruptions to the power supply. SETTING: Health centres in Colombo District. METHOD: An interviewer-administered questionnaire was used to collect information on staff compliance with regulations of the expanded program of immunisation (EPI) and alternative facilities available for refrigeration during power failure. The refrigerator and storage conditions were inspected. The stored vaccines were tagged with thermosensitive cold chain monitors, which were read on revisiting the clinic 14 days later. During the study period, power cuts of 2 hours' duration were in force daily. A control study was carried out when there was no interruption to power supply. RESULTS: Diphtheria-pertussis-tetanus (DPT) and measles vaccines had been exposed to temperatures outside the prescribed range during power cuts. Oral polio vaccine had adequate storage with power cuts of 2 hours' duration. CONCLUSION: Alternative facilities for vaccine storage during power cuts were not available and the potency of DPT and measles vaccines were compromised with interruptions to power of 2 hours' duration or more.

Drug Storage↗

[A survey on vaccine efficacy in the city of Bongor (Chad) and its operational consequences for the vaccination program].

A measles epidemic occurred in the city of Bongor, Chad, from 22 September 1993 to 26 June 1994. A total of 792 patients were hospitalized, with a case fatality rate of 5.2%. After the epidemic, the district management team evaluated the expanded programme on immunization (EPI). Through a cluster survey the attack rate was estimated to be 29.1% (95% confidence interval (CI) = 20.4-37.8%) for the age group 12-59 months (n = 206). For this same age group, the measles immunization coverage was estimated to be 44.2% (95% CI = 34.6-53.8%) and the vaccine efficacy 9.5% (95% CI = 0-41.5%). Several flaws in the logistic handling of the vaccines and especially in the cold chain were identified. These results indicated a serious management problem in the EPI, which the district team then immediately started to rectify. The method used to estimate the immunization coverage and efficacy in the study is rapid and low cost. Also, it is feasible at the district level and permits identification of management problems in the EPI.

Age Factors↗

Subunit vaccines for the control of tick-borne diseases: implications for the future.

Tick-borne parasites are a major constraint to the improvement of livestock productivity in the developing world. These parasites include Theileria parva, T. annulata, Babesia bigemina, B. bovis, Anaplasma marginale and Cowdria ruminantium. The impact of these diseases is currently limited by the use of acaricides to decrease transmission by the tick vectors and immunization of the host animals using live vaccines. The use of acaricide is hampered by the development of acaricide resistance and live vaccines are dependent on cold chain facilities, which are generally unreliable in developing countries. There is therefore a requirement for improved vaccines that circumvent these problems. Candidate vaccine antigens have been identified for most of these parasites and are currently being evaluated for their capacity to induce solid protection.

Anaplasma↗

[The risk of transmission of salmonellae in poultry farming: detection and prevention in Europe].

While salmonellas can cause disease problems among poultry, they remain essentially a concern for public health, as a cause of outbreaks of food poisoning. The principal site of multiplication of these bacteria is the digestive tract, particularly the caecum, which may result in widespread contamination of the environment. The pathogenicity of salmonellas depends on the invasive properties and the ability of the bacteria to survive and multiply within cells, particularly macrophages. These properties are the source of vertical transmission which, in the case of survival of the embryo, can result in contamination of a flock or, in the case of embryonic mortality, can result in an explosion of contaminated eggs. Salmonella infection can be diagnosed by isolating the bacteria and/or serological testing of the flock. European Union Directive 92/117/EC, modified by Directive 97/22/EC, stipulates either the destruction of infected flocks of breeding birds, or decontamination of the flock in an effective way, before normal trade in products can be resumed. Noteworthy examples of effective measures suitable for prophylaxis of Salmonella infection in poultry flocks include the slaughter of infected breeding stock, the creation of sanitary barriers at building entrances, heat treatment of feed, the use of competitive exclusion, selection of breeds genetically resistant to Salmonella, and occasional vaccination and antibiotic treatment. However, the most effective means of reducing food poisoning remains adequate cooking of food and maintenance of the cold chain.

Animals↗

Rehabilitation of the expanded programme on immunization in Sudan following a poliomyelitis outbreak.

In 1993 a large outbreak of paralytic poliomyelitis occurred in Sudan as a result of an accumulation of large numbers of susceptible children that was accelerated by faltering immunization services. The extent of the outbreak led to the rapid rehabilitation of Sudan's Expanded Programme on Immunization (EPI); the government began financing vaccine purchase, operational aspects of EPI were decentralized, vaccine delivery was changed from a mobile to a fixed-site strategy, a solar cold chain network was installed, inservice training was resuscitated, and social mobilization was enhanced. National immunization days (NIDs) for poliomyelitis eradication were conducted throughout the country, including the southern states during a cease fire in areas of conflict. Measles immunization coverage was increased by offering measles vaccine during the second round of NIDs and subsequently through routine immunization services. Supplemental tetanus toxoid immunization of women of child-bearing age began in three provinces at high risk for neonatal tetanus. From 1994 to 1996 reported immunization coverage increased and the incidence of all EPI target diseases fell. Trends in coverage, disease incidence, financing, and the implementation of WHO-recommended disease-control strategies suggest that more sustainable immunization services have been re-established in Sudan.

Adult↗

Light-chain heterogeneity of cold agglutinins.

Cold agglutinins with specificity to I or to i antigens of humanadult or cord-blood erythrocytes produced during the course of Mycoplasma pneumoniae infection and infectious mononucleosis contain light chains of K and L types. However, cold agglutinin isolated from the serums of patients with chronic cold-agglutinin hemolytic anemia contains only type K light chains. The experimental evidence suggests that some cold agglutinins contain both types of light chains in the same molecule.

Anemia, Hemolytic↗

The sugar chains of cold-insoluble globulin. A protein related to fibronectin.

Cold-insoluble globulin isolated from bovine plasma contains six asparagine-linked sugar chains in 1 molecule (a dimeric form). These sugar chains were released from the polypeptide backbone by hydrazinolysis and labeled by reduction with NaB[3H]4. Most of these sugar chains contain N-acetylneuraminic acid and can be separated by paper electrophoresis. By combination of sequential exoglycosidase digestion and methylation study, their structures were elucidated as Gal beta 1 leads to 4GlcNAc beta 1 leads to 2Man alpha 1 leads to 6(NeuAc alpha 2 leads to 6Gal beta 1 leads to 4GlcNAc beta 1 leads to 2Man alpha 1 leads to 3)Man beta 1 leads to 4GlcNAc beta 1 leads to 4GlcNAc, NeuAc alpha 2 leads to 6 or 4Gal beta 1 leads to 4GlcNAc beta 1 leads to 2Man alpha 1 leads to 6(NeuAc alpha 2 leads to 4 or 6Gal beta 1 leads to 4GlcNAc beta 1 leads to 2Man alpha 1 leads to 3)Man beta 1 leads to 4GlcNAc beta 1 leads to 4GlcNAc, NeuAc alpha 2 leads to 6Gal beta 1 leads to 4GlcNAc beta 1 leads to 2Man alpha 1 leads to 6[NeuAc alpha 2 4Gal beta 1 leads to 3(NeuAc alpha 2 leads to 6)GlcNAc beta 1 leads to 2Man alpha 1 leads to 3]-Man beta 1 leads to 4GlcNAc beta 1 leads to 4GlcNAc and NeuAc alpha 2 leads to 4Gal beta 1 leads to 3(NeuAc alpha 2 leads to 6)GlcNAc beta 1 leads to 2Man alpha 1 leads to 6[NeuAc alpha 2 leads to 4Gal beta 1 leads to 3(NeuAc alpha 2 leads to 6)GlcNAc beta 1 leads to 2Man alpha 1 leads to 3]man beta 1 leads to 4GlcNAc beta 1 leads to 4GlcNAc.

Animals↗

Restriction in the repertoire of the immunoglobulin light chain subgroup in pathological cold agglutinins with anti-Pr specificity.

BACKGROUND AND OBJECTIVES: In cold agglutinin disease, monoclonal red blood cell autoantibodies, termed cold agglutinins, induce haemolysis in patients exposed to the cold. Commonly, these autoantibodies are directed against the developmentally regulated I/i blood groups. A second blood group system, the Pr system (located on glycophorins), is involved less frequently. Anti-Pr cold agglutinins recognize either alpha 2,3- or alpha 2,6-linked N-acetylneuraminic acid as the immunodominant group. Cold agglutinins of anti-I/i specificity show a remarkable restriction in their genomic repertoire of the immunoglobulin heavy and light-chain immunoglobulin-variable domain (i.e. exclusive use of VH4-34 in heavy chains). For anti-Pr cold agglutinins, preliminary data on the repertoire of the light-chain variable domain indicate a preference for the subgroup Vkappa IV. To elucidate restrictions in the light-chain variable-domain subgroup repertoire of anti-Pr cold agglutinins systematically, and to discuss these results in the context of their anti-Pr(1-3) subclassification and immunodominant sialic acid, light chains in 13 anti-Pr cold agglutinins were investigated. MATERIALS AND METHODS: The anti-Pr light chains were isolated using temperature-dependent absorption/elution techniques. Subsequently, they were subjected to N-terminal Edman degradation, and the light chain Vkappa subgroup was affiliated using the Kabat database. RESULTS: Five of 13 (38%) light chains belonged to Vkappa IV, five of 13 (38%) to Vkappa I and three of 13 (23%) to Vkappa III. Anti-Pr with Vkappa IV subgroup light chains exclusively recognized alpha 2,3-linked N-acetylneuraminic acid. CONCLUSIONS: Including data from the literature, the repertoire of the light-chain variable domain in pathological anti-Pr cold agglutinins exhibits a clear bias towards the use of the single germline gene-derived subgroup, Vkappa IV (eight of 17 or 47%). The association of Vkappa IV subgroup light chain-containing anti-Pr cold agglutinins with binding to alpha 2,3-, but not alpha 2,6-linked N-acetyneuraminic acid raises speculations about a possible role of subgroup-derived determinants in anti-Pr binding.

Adult↗

Plasma branched-chain amino acids in cold- and heat-acclimatised rats.

The concentrations of plasma branched-chain amino acids, valine, isoleucine and leucine, were significantly elevated in cold-acclimatised rats, while these values were significantly reduced in heat-acclimatised rats, in both 2-week and 4-week temperature acclimatisation.

Acclimatization↗

Light chain sequences of human IgM cold agglutinins (variable-region subgroups amino-acid sequence-kappa light chain-N-terminal).

The amino-terminal amino-acid sequence has been determined for the kappa light chains of nine IgM cold agglutinins with specificity for blood group-related carbohydrate antigens. Six of the nine sequences corresponded to the prototype VK(III) subgroup pattern, two to that of subgroup VK(II), and only one to the VK(I) subgroup. This distribution of kappa subgroups differs markedly from that of normal and myeloma proteins sequenced to date, where the VK(I) subgroup is more prevalent than either VK(II) or VK(III). Evidence is presented that supports the conclusion that the unusual subgroup distribution relates to the antibody property itself and not to some other attribute of these molecules.

Amino Acid Sequence↗

Inducible cell ablation in Drosophila by cold-sensitive ricin A chain.

We have developed a system for temperature-inducible killing of specific cells in the fruitfly Drosophila melanogaster. The system overcomes many of the limitations of existing cell ablation methods and is in principle applicable to any non-homeothermic eukaryote. Temperature-sensitive and cold-sensitive mutations in the ricin toxin A chain (RTA) of castor bean were generated in yeast. One cold-sensitive mutation, RAcs2, produced temperature-dependent ablation of eye cells in Drosophila when expressed under control of the eye-specific sev enhancer. At 29 degrees C, cell death was observed within 7 hours in the developing eye and no obvious toxic effects were observed elsewhere; at 18 degrees C, extremely low toxicity was observed. DNA sequencing of RAcs2 revealed a single amino acid substitution in the RTA active site cleft.

Animals↗

[A study on the peripheral circulatory function and on the cold pressor response in chain saw operators (author's transl)].

Among the vibration hazards resulting from the use of vibrating tools, Raynaud's phenomenon, the peripheral nervous disturbances and the bone-joint abnormalities have been well known. Especially, Raynaud's phenomenon, which is explained as a spasm of the peripheral vascular vessels caused by disorders of the peripheral nerves or abnormalities of the arteriolae, represents the peripheral circulatory disturbance. In the worker with such a disorder of the peripheral circulatory function, it is likely that the mechanism of the cold pressor response would have been changed. The authors examined the relationship between the peripheral circulatory function and the cold pressor response in 51 chain saw operators. The following examinations were carried out: skin temperature, nail-press test and cold pressor test by 10-minute-immersion in 10 degrees C water. There was statistically an inverse correlation (r=-0.316, P < 0.025) between the increase in systolic blood pressure at the second minute during immersion and the mean skin temperature of the finger-tip during the latter half of 10-minute-immersion. It would be surmised from this result that the worker with lower peripheral circulatory function tends to increase the excitability in the sympathetic nervous system.

Adult↗

Correlation of long-range membrane order with temperature-dependent growth characteristics of parent and a cold-sensitive, branched-chain-fatty-acid-deficient mutant of Listeria monocytogenes.

Listeria monocytogenes is a food-borne, pathogenic, psychrotolerant bacterium that grows at refrigeration temperatures. Long-range membrane order of the parent (10403S) and of a cold-sensitive mutant ( cld-1) deficient in odd-numbered, branched-chain fatty acids was measured using the width of the central line of spectra of an electron paramagnetic resonance probe, 4,4-dimethyl-2-heptyl-2-hexyloxazolidine- N-oxyl (7N14), that locates deep in the hydrocarbon region of the membranes. The line width decreased from 0.9 to 0.5 milliTesla (mT) over the temperature range of 0-10 degrees for strain 10403S and -5 to 32 degrees C for strain cld-1 independent of protein state (heat denatured or intact). This provided new evidence for phase transitions in the membranes. When strain cld-1 was grown in medium supplemented with 2-methylbutyric acid, which restores anteiso fatty acids and the ability to grow at low temperature, the change in central line width as a function of temperature resembled that of strain 10403S. The temperatures at which the central line width became 0.8 mT corresponded to those at which growth became very slow in both strains (3-5 degrees C for 10403S, 15 degrees C for cld-1) as determined by Arrhenius plots. These data underscore the critical role of odd-numbered anteiso fatty acids in influencing the lower temperature limits of growth through their effects on long-range membrane fluidity.

Butyric Acid↗