This datasheet on Hexamita covers Identity, Distribution, Hosts/Species Affected.

The measles virus is highly contagious and may hit non-immune populations very hard, as observed on remote islands. The first live-attenuated measles virus vaccine was registered in the United States in 1963, and was imported to the Netherlands from 1968 onwards. Production was taken over by the National Institute for Public Health (RIV). Because the burden of disease was still high, measles vaccination was introduced into the Dutch National Immunisation Programme in 1976; since 1987 this has been in the form of the combined measles, mumps and rubella (MMR) vaccination. The MMR vaccine was also initially imported and later manufactured by the National Institute for Public Health and the Environment (RIVM). Since then, measles epidemics have almost exclusively affected unvaccinated populations. Vaccinated individuals are thus well-protected, as are unvaccinated individuals as long as the rate of vaccination in the surrounding population is sufficiently high. Unvaccinated individuals who travel to countries where measles is endemic are still at a higher risk. Recent studies show that measles not only has the classical symptoms, but also damages the immune system.

After a development period of around 13 years, in 1993 the vaccination against infections caused by Haemophilus influenzae type b (Hib) was introduced into the Dutch National Immunisation Programme. Before the introduction of the vaccination, the burden of disease was high; every year around 700 children acquired an invasive Hib infection, half of whom developed meningitis. Of those children with Hib-related meningitis, 2% died and more than 8% were left with severe residual symptoms. Furthermore, at least one-third of those who recovered developed learning and concentration problems. Hib also caused other infections such as epiglottitis, osteomyelitis and arthritis. Initially, the conjugated Hib vaccine PRP-T was given as a separate injection. From 2005 onwards PRP-T was included in the combination DTaP-IPV-Hib vaccine, and since 2011 PRP-T has been part of the DTaP-IPV-Hib-HepB vaccine. Although H. influenzae is still around, invasive Hib infections in children now occur only very rarely.

This literature review identifies the factors that influence the decision to introduce inactivated polio vaccine (IPV) in developing countries as opposed to the policy of vaccine cessation. Attenuated viruses in the oral polio vaccine (OPV) can replicate, revert to neurovirulence and become transmissible circulating vaccine-derived polioviruses (cVDPVs), preventing use of the vaccine in the post-eradication era. This literature review identifies (1) risks of complete cessation of vaccination, (2) barriers and (3) solutions for the introduction of IPV in developing countries. The reviewed literature favours to circumvent the so-called “OPV paradox” by global introduction of IPV.

Summary A group of 7 female calves was injected with 80 mg. diethylstilbestrol (DES) at an age of 8 weeks. Seven animals were kept as controls. One week after the administration of DES 4 animals from the experimental group received an intramuscular injection of alum-adsorbed tetanus toxoid. A booster injection was given 2 weeks later. Autopsy was performed at an age of 16 weeks. No influence from the estrogen treatment on the immune response could be detected. Zusammenfassung Einfluß von Östrogenen auf die Immunitätsbildung Eine Gruppe von 7 weiblichen Mastkälbern, die mit 80 mg Diäthylstilböstrol (DES) vorbehandelt worden waren, wurden im Alter von 8 Wochen untersucht. Sieben Tiere dienten als Kontrolle. Eine Woche nach der Verabreichung von DES erhielten 4 Tiere alum-adsorbiertes Tetanustoxoid injiziert. Eine zweite Injektion folgte nach 2 Wochen. Im Alter von 16 Wochen wurden die Tiere geschlachtet. Es konnte kein Effekt auf die immunologische Reaktion der Kälber festgestellt werden.

Summary The effect of various oestrogens was studied in male calves. The following oestrogens were used: diethylstilboestrol (in dosages of 20, 50 and 80 mg.), hexoestrol (80 and 160 mg.), dienoestrol (80 mg.) and oestradiol monobenzoate (80 mg.). The histological reaction of the prostate was studied in short term experiments (1–21 days after administration of the oestrogen) and long term experiments (8, 9, and 12 weeks after administration of the oestrogen). The oestrogens were injected both intramuscularly and subcutaneously. In the prostates of all treated animals, hyperplastic and metaplastic changes were observed. These changes were not influenced by the simultaneous application of a weak androgen (Laurabolin). Besides the parenteral administration the influence of orally administered diethylstilboestrol on the prostate was studied. Again the prostate reacted with hyperplasia and metaplasia. Zusammenfassung Auswertung des “Prostata-Tests” beim Nachweis der Oestrogenapplikation an Kälbern Bei Stierkälbern wurde die Wirkung verschiedener Oestrogene untersucht. Folgende Oestrogene wurden geprüft: Diäthylstilböstrol (Dosis: 20, 50, 80 mg), Hexöstrol (80, 160 mg), Dienöstrol (80 mg) und Oestradiolmonobenzoat (80 mg). Die histologischen Reaktionen der Prostata wurden in kurzdauernden (1–21 Tage) sowie langdauernden (8, 9 und 12 Wochen) Experimenten studiert. Die Oestrogene wurden sowohl intramuskulär als auch subkutan appliziert. Bei allen Tieren traten hyperplastische und metaplastische Veränderungen auf. Diese Veränderungen wurden durch die gleichzeitige Verabreichung eines schwachen Androgens (Laurabolin) nicht beeinflußt. Außer der parenteralen Verabreichung wurde auch der Einfluß der oralen Applikation von Diäthylstilböstrol auf die Prostata geprüft. Auch in diesen Versuchen reagierte die Prostata mit einer Hyperplasie und Metaplasie. Résumé Evaluation du après administration d'oestrogènes chez le veau On étudie les effets de différents oestrogènes sur des veaux mâles. On emploie les oestrogènes suivants: diéthylstilboestrol (en doses de 20, 50 et 80 mg), hexoestrol (80 et 160 mg), diènoestrol (80 mg) et le monobenzoate d'oestradiol (80 mg). On suit la réaction histologique de la prostate dans des expériences à court terme (1–21 jours après administration de l'oestrogène) et à long terme (8, 9 et 12 semaines après administration de l'oestrogène). On injecte les oestrogènes par voie intramusculaire et sous-cutanée. On observe des modifications hyperplastiques et métaplasiques dans la prostate de tous les animaux traités. Ces modifications ne sont pas influencées par l'application simultanée d'un androgène faible (Laurabolin). Après étude des effets de l'administration parentérale, on étudie l'influence du diethylstilboestrol administré per os sur la prostate. La prostate réagit également par und hyperplasie et une métaplasie. Resumen Evaluación de la en la búsqueda de la administración de estrógenos a terneros Estudióse el efecto de varios estrógenos en terneros. Se usaron los estrógenos siguientes: dietilestilbestrol (en dosis de 20, 50 y 80 mg), hexestrol (80 y 160 mg), dienestrol (80 mg) y monobenzoato de estradiol (80 mg). La reacción histológica de la próstata se analizó en experimentos de fecha proxima (1–21 días después de administrar el estrógeno) y en experiencias a plazo largo (8, 9 y 12 semanas tras la administración de los estrógenos). Las substancias se inocularon tanto intramuscular como subcutáneamente. En la próstata de todos los animales tratados se observaron cambios hiper- y metaplásicos. Estos cambios no fueron influídos por la aplicación simultánea de un andrógeno catabólico (Laurabolin). Al lado de la administración parenteral, se estudió el influjo del dietilestilbestrol, administrado por vía oral, sobre la próstata. De nuevo, la próstata reaccionó con hiper- y metaplasia.

To date, the policy to control hepatitis B in the Netherlands is to vaccinate specific risk groups, rather than all children. Low incidence of the disease has fueled debate whether such a targeted vaccination strategy or rather a universal strategy, as recommended by the World Health Organization, is appropriate. The standard framework for assessing whether a particular vaccination should be included in a public programme, as recently proposed by the Health Council of the Netherlands (HCN), was applied to the various options for hepatitis B vaccination. This framework includes seven selection criteria, grouped under five thematic headings: seriousness and extent of the disease burden, effectiveness and safety of the vaccination, acceptability of the vaccination, efficiency of the vaccination, and priority of the vaccination. From about 1990 the disease burden has stayed more or less the same over time and careful assessment has made it clear that the targeted approach has failed to reach a significant part of the risk groups. Models suggest that the public health benefits obtained through targeted programmes could be augmented considerably by universal vaccination. Based on the assessment that universal vaccination means better protection for high-risk groups as well as the whole population, the HCN calls for universal immunisation, even though hepatitis B to a large extent is limited to specific high-risk groups. Should the Netherlands adopt universal vaccination, several immunisation programmes targeted to high-risk groups will, however, remain of crucial importance for years to come.

Summary The changes in the genital tract of the female calf after the administration of two estrogens, diethylstilbestrol and hexestrol, at the age of 8 weeks were investigated. At slaughter at the age of 16 weeks alterations were found in the tuba, the cervix, the vagina, the glands of Bartholin and the mammary glands. The changes are similar to those found during estrus. All animals which had received DES showed changes in all organs at slaughter with the exception of the tuba, where only 40 out of 50 animals displayed alterations. In animals which had received HEX only the glands of Bartholin showed alterations in all animals while changes in the other organs could be found in only some of the animals. In the genital tract of 225 female calves slaughtered at various slaughterhouses in the Netherlands, no alterations could be observed in the cervix and the glands of Bartholin, indicating that these animals had not been treated with estrogens. The histological examination of the glands of Bartholin is proposed as a method to determine the administration of estrogens to female fattening calves. Zusammenfassung Histologische Veränderungen am Genitaltrakt des weiblichen Kalbes nach der Applikation von Diäthylstilböstrol und Hexöstrol Es wurden die Veränderungen am Genitaltrakt weiblicher Kälber nach der Verabreichung von zwei Oestrogenen (Diäthylstilböstrol, Hexöstrol) im Alter von 8 Wochen untersucht. Bei der Schlachtung im Alter von 16 Wochen wurden Veränderungen am Eileiter, an der Zervix, an der Vagina, an den Bartholinischen Drüsen und an der Milchdrüse gefunden. Die Veränderungen sind denen während der Brunst ähnlich. Alle Tiere, welche Diäthylstilböstrol erhielten, zeigten mit Ausnahme des Eileiters an allen Organen Veränderungen. Am Eileiter konnten nur in 40 von den 50 Tieren Alterationen festgestellt werden. Bei den Tieren, welche Hexöstrol erhielten, wiesen nur die Bartholinischen Drüsen bei allen Tieren Veränderungen auf. Nur einige Tiere zeigten auch an den andern Organen Veränderungen. Am Genitaltrakt von 225 weiblichen Kälbern, welche an verschiedenen Orten der Niederlande geschlachtet wurden, konnten Alterationen weder an der Zervix noch an den Bartholinischen Drüsen festgestellt werden, was dafür spricht, daß die Tiere nicht mit Oestrogenen behandelt wurden. Die histologische Untersuchung der Bartholinischen Drüsen kann als Test für eine Oestrogenisierung weiblicher Kälber zum Zwecke der Mastförderung angewendet werden. Résumé Modifications histologiques du tractus génital chez le veau femelle, après administration de diéthylstilboestrol et d'hexoestrol On examine les modifications du tractus génital de veaux femelles après administration de deux oestrogènes (diéthylstilboestrol, hexoestrol) à l'âge de 8 semaines. Après abattage à l'âge de 16 semaines, on trouve des modifications des oviductes, du cervix, du vagin, des glandes vulvo-vaginales et des glandes mammaires. Les modifications ressemblent à celles que l'on observe pendant le rut. Tous les animaux ayant reçu du diéthylstilboestrol présentent des modifications dans tous les organes, à l'exception des oviductes. On ne trouve des modifications des oviductes que chez 40 sur 50 animaux. Chez les veaux ayant reçu de l'hexoestrol, seules les glandes vulvo-vaginales présentent des modifications constantes. Quelques animaux seulement ont des modifications dans les autres organes. En examinant le tractus génital de 225 veaux femelles abattus dans différents endroits des Pays-Bas, on n'a trouvé des modifications ni dans le cervix, ni dans les glandes vulvo-vaginales, ce qui signifie que les animaux n'ont pas été traités aux oestrogènes. L'examen histologique des glandes vulvo-vaginales peut donc servir de test pour mettre en évidence l'oestrogénisation des veaux femelles à des fins d'engraissement. Resumen Alteraciones histológicas en el tracto genital de terneras tras la aplicación de dietilestilbestrol y hexestrol Se estudiaron las alteraciones producidas en el tracto genital de terneras tras la administración de dos estrógenos (dietilestilbestrol, hexestrol) a la edad de 8 semanas. Tras el sacrificio a las 16 semanas de edad, se hallaron transformaciones en la trompa de Falopio, cuello del útero, vagina, glándulas de Bartholin y en la glándula mamaria. Las alteraciones son semejantes a las apreciadas durante el celo. Todos los animales que recibieron dietilestilbestrol presentaban alteraciones en todos los órganos, excepción hecha por la trompa de Falopio. En esta última, solo en 40 de 50 animales se pudieron reconocer modificaciones. En los animales que recibieron hexestrol, solo las glándulas de Bartholin presentaron alteraciones en todos los animales. Pocas terneras nada más también mostraban alteraciones en otros órganos. En el tracto genital de 225 terneras, que fueron sacrificadas en los más diversos puntos de los Países Bajos, no se pudieron apreciar modificaciones ni en el cuello del útero ni en las glándulas de Bartholin, lo cual aboga a favor de que estos animales no fueron sometidos a estrógenos. El examen histológico de las glándulas de Bartholin se puede utilizar como prueba elucidativa de la estrogenizacion de terneras con fines de fomentar el engorde.

As more and more new vaccines are developed and brought to the market, governments have to make decisions about which vaccinations to include in public programmes. This paper describes the experience in the Netherlands in developing a framework for assessing whether a vaccination should be included in the National Immunization Programme (NIP). Bearing in mind the public nature, the factors that determine a vaccine's suitability for inclusion in a communal vaccination programme have been translated into seven selection criteria, grouped under five thematic headings: seriousness and extent of the disease burden, effectiveness and safety of the vaccination, acceptability of the vaccination, efficiency of the vaccination, and priority of the vaccination. The seven criteria and the explanation of them provide a framework for the systematic examination of arguments for and against the inclusion and prioritisation of particular vaccinations. As an illustration, the vaccinations currently provided in the Netherlands through public programmes as well as 23 'candidate' vaccinations are assessed against the seven criteria. The proposed assessment framework including the selection criteria can take full account of the values and specificities as they may differ between situations and countries; the transparency of the approach may help to clarify which elements of the assessment are pivotal in specific situations. Using the criteria furthers a trustworthy, transparent and accountable process of decision-making about inclusion of new vaccinations in public vaccination programmes and may help to retain public confidence.

Aims: The study was conducted to evaluate the possibility of selecting convalescent diphtheria patients to serve in emergency situations as donors for the production of anti-diphtheria immunoglobulin. To select suitable donors, the criterion of an antitoxin titer ≥3.0 IU/ml was used. In addition, the effects of treatment and the effect of immunization with diphtheria toxoid on the level of anti-diphtheria toxin antibodies were evaluated. Scope: Three groups of diphtheria patients were included in the study. The first group (n=23) consisted of patients who had a basic antibiotic treatment, with or without serotherapy using horse antitoxin and/or human immunoglobulin. The second group (n=12) comprised patients examined immediately after the onset of disease. The immunological history of this group was not known. The third group (n=20) included patients with a known immunization history, treated only with antibiotics but having received a booster immunization with diphtheria toxoid. Antitoxin titers were measured using the toxin binding inhibition (ToBI) assay. Conclusions: In the first group, 47.8% (11/23) of the patients had a diphtheria antibody titer ≥3.0 IU/ml. For most of them, however, the antibody titers could have resulted from treatment with exogenous antibodies from horse antitoxin or human immunoglobulin (18/23). Only two of the 11 high-titer subjects had received antibiotics only. Among the second group, only two (16.76%) of the patients had an antibody titer of ≥3.0 IU/ml. In the third group 50% (10/20) of the patients showed an antibody titer of ≥3.0 IU/ml prior to vaccination, and therefore could be directly considered as donors. Three weeks after booster vaccination, 70% (14/20) had an antibody titer of ≥3.0 IU/ml and 1 year after booster vaccination, 28.6% (2/7) of the subjects still had titers of ≥3.0 IU/ml. In 40% of these patients, a decrease was observed 3–4 weeks after the booster dose. It was concluded that convalescent diphtheria patients could be considered as donors in an emergency situation, since approximately half of them showed antitoxin titers of ≥3.0 IU/ml.

In this report we present studies on optimal regimes for regional IL-2 therapy, focused on dose, schedule and site of injection. Original data obtained in 2 murine tumour models show that all 3 factors are of importance. Anti-tumour responses were most effective when IL-2 was administered regionally 5 to 10 times, at doses ranging from 7,000 to 33,000 IU/day every day or every other day. This resulted in cure rates of more than 40% in mice bearing ascitic tumour that had also disseminated to liver and lungs. The importance of these data is discussed in the light of previous results of our group. These results illustrate that the doses and schedules used in this study are not effective exclusively in these 2 tumour models but may have a more general applicability.

Protective immunity to leishmaniasis has been demonstrated in murine models to be mediated by T cells and the cytokines they produce. We have previously shown that resistance to experimental Leishmania infantum infection in the dog, a natural host and reservoir of the parasite, is associated with the proliferation of peripheral blood mononuclear cells (PBMC) to parasite antigen and to the production of interleukin-2 and tumour necrosis factor. In this study we show that PBMC from asymptomatic experimentally infected dogs produce interferon-gamma upon parasite antigen-specific stimulation, whereas lymphocytes from symptomatic dogs do not. In addition, we report for the first time the lysis of L. infantum-infected macrophages by PBMC from asymptomatic dogs and by parasite-specific T cell lines derived from these animals. These T cell lines were generated by restimulation in vitro with parasite soluble antigen and irradiated autologous PBMC as antigen-presenting cells. We show that lysis of infected macrophages by T cell lines is major histocompatibility complex restricted. Characterization of parasite-specific cytotoxic T cell lines revealed that the responding cells are CD8+. However, for some animals, CD4+ T cells that lyse infected macrophages were also found. In contrast to asymptomatic dogs, lymphocytes from symptomatic dogs failed to proliferate and produce interferon-gamma after Leishmania antigen stimulation in vitro and were not capable of lysing infected macrophages. These results suggest that both the production of interferon-gamma and the destruction of the parasitized host cells by Leishmania-specific T cells play an important role in resistance to visceral leishmaniasis.

We have tested the therapeutic potency of peritumorally injected low doses of interleukin-2(IL-2). Seventy tumours of the bovine ocular squamous-cell carcinoma (BOSCC), 1–3 cm in diameter, were treated with 5000, 20 000 or 200 000 U IL-2 from Eurocetus (Chiron) to find the optimal dose for treatment. Injections were given peritumorally on Monday to Friday on 2 consecutive weeks. The size of the tumours was measured before treatment and 1, 3, 4, 9 and 20 months after treatment. After 9 months complete regression was observed in 89% of the tumours treated with 5000 U IL-2, 80% treated with 20 000 U and 67% treated with 200 000 U. After 20 months, there was complete regression of 35%, 31% and 67% of the tumours respectively. The 9-and 20-month results of the 200 000-U treatment are significantly better than those of the 5000-U and 20 000-U treatments taken together. This protocol may be useful to treat advanced inoperable tumours (e.g. of the nasopharynx or skin) of human patients.

Thirty cows from a pedigree Friesian dairy herd with bovine vulva papilloma and carcinoma were treated by intralesional injections of live bacillus Calmette-Guérin (BCG). This treatment induced total regression of all of six carcinomas. Whilst, after treatment, limited regression was also observed in advanced papillomas, BCG has little or no effect on the early stages of papillomas. This is the first study of BCG therapy in this type of cancer.

In many human clinical trials and in various animal tumor models, the antitumor effect of high doses of systemically applied interleukin-2 (IL-2) is tested. Our studies focused on the effects of low doses of locally injected IL-2. In this paper, the effect of local injection of low doses of IL-2, i.e. a total dose of 25,000-50,000 units, into papillomas or carcinomas of the bovine vulva is described. In 19 out of 23 (83%) cows treated with IL-2 an effect on the tumor load was observed; in three of these animals, complete regression was obtained. In the majority of cases, regression was not restricted to the tumors injected with IL-2.

Although the cause of bovine ocular squamous cell carcinoma (BOSCC) is attributed to viruses in addition to cofactors (eg, UV light), to our knowledge, the final causative agent has not been described. Bovine papilloma virus (BPV)-like particles were detected in approximately 33% of various putative precursor lesions of BOSCC. In contrast, it was reported that, using BPV-specific antibodies, it was not possible to detect viral antigens in BOSCC. Fourteen established BOSCC and 9 BOSCC-derived cell lines were examined for BPV DNA. Probes of all 6 known BPV types were used in various hybridization assays. Neither Southern blot analysis, under high and low stringency conditions, nor in situ hybridization resulted in detection of BPV DNA. Papilloma viruses were not observed in electron microscopic studies. Results exclude direct association between BOSCC and BPV types 1 to 6, or as yet unknown closely related BPV types. However, BPV may contribute to induction of precursor lesions or events leading to carcinogenic transformation, without being relevant for maintenance of the tumor.

To study the local immunological effects of intravesical bacillus Calmette-Guérin (BCG) therapy in superficial bladder cancer patients, the production of interleukin-1 (IL-1), IL-2, IL-6, tumour necrosis factor α (TNFα), and interferon γ (IFNγ) was investigated in the urine. Urine specimens were collected during the six weekly BCG instillations, before instillation, and 2, 4, 6, 8, and 24 h thereafter. Results were standardized to urine creatinine. In general, the concentration of IL-1 increased markedly during the first three BCG instillations, reaching a plateau from instillations 3 to 6. IL-2 was not detected after the first BCG instillation, but from the second instillation onwards the mean IL-2 concentration increased rapidly. With respect to IL-6, patients had relatively high levels in the urine after the first BCG instillation. A relatively moderate increase of the IL-6 concentration was observed during the following weeks. Like IL-2, TNFα was only detected after repeated BCG instillations. Generally the highest TNF levels were found after BCG instillation 5. The presence of IFNγ could not be demonstrated. With respect to the occurrence of the cytokines during the first 24 h after the BCG instillation, TNF, IL-2, and IL-6 were detectable 2 h after the instillation. In contrast, IL-1 seemed to appear later, i.e. from 4 h onwards. TNF decreased most rapidly; it was nearly absent in 6-h samples. Generally IL-2 was not detectable in the 8-h samples, whereas IL-1 and IL-6 were present up to 8 h after instillation of BCG. The presence of TNF was found less frequently than the presence of IL-1, IL-2, and IL-6. Neutralization experiments indicated that most of the IL-1 present in the urine after BCG treatment was IL-1α. In conclusion, activation of BCG-specific T cells was indicated by the detection of IL-2. The presence of IL-1, IL-6, and TNFα might suggest activation of macrophages by intravesically administered BCG, although production by other cell types cannot be excluded. It is suggested that these cytokines, in combination with the leucocytes that are known to be recruited to the bladder in reaction to the BCG treatment, may play an important role in the antitumour activity of BCG against bladder cancer. For monitoring purposes, collection of urine might be performed during the first 6 h after BCG instillations 4–6. A correlation between the presence of cytokines in the urine and the clinical response has yet to be evaluated.