Tetanus, diphtheria, and acellular pertussis vaccine coverage in adults with chronic respiratory conditions.

BACKGROUND: Pertussis is a highly contagious respiratory disease, and those with chronic respiratory illnesses may be at higher risk of infection and severe pertussis. Acellular pertussis-containing vaccines (Tdap) are recommended in the United States for those with risk factors, such as asthma and chronic obstructive pulmonary disease (COPD). OBJECTIVE: To determine Tdap vaccination rates among people with asthma or COPD compared with matched controls with type 2 diabetes and the general population. METHODS: This observational database study identified adults with asthma or COPD, and their matched controls, from a large US administrative health claims system between January 2008 and December 2014. Vaccination with Tdap was identified using current procedural terminology and national drug codes, and vaccination rates per 1000 patient-years and adjusted rate ratios (RR) were calculated using a generalized linear model with a Poisson distribution and 95% confidence intervals (CI). RESULTS: Vaccination rates were low overall; however, they were slightly higher in asthma than the general population cohort, with vaccination incidence RRs of 1.12 (95% CI, 1.08-1.17), 1.09 (95% CI, 1.06-1.11), and 1.11 (95% CI, 1.07-1.16) in those aged 18 to 44, 45 to 64, and 65 years and older, respectively. However, Tdap vaccination rates were lower in the COPD than in the general population cohort, with vaccination incidence RRs of 0.72 (95% CI, 0.60-0.86), 0.87 (95% CI, 0.83-0.91), and 0.94 (95% CI, 0.92-0.96), respectively. CONCLUSION: Pertussis vaccination rates were suboptimal among adults in general and adults with asthma or COPD. Work is needed to boost Tdap vaccination uptake among people with chronic respiratory conditions.

Sequential rituximab therapy sustains remission of nephrotic syndrome but carries high risk of adverse effects.

BACKGROUND: Sequential rituximab (RTX) administration has emerged as an important strategy to sustain remission of disease in patients with difficult-to-treat nephrotic syndrome. METHODS: We report the efficacy and safety of sequential therapy with two or more courses of intravenous RTX in 250 patients with difficult-to-treat steroid dependence (n = 127) and calcineurin inhibitor (CNI)-dependent or CNI-refractory steroid resistance (n = 123) managed at one center during 2015-2021. Subsets of patients were cross-sectionally tested for hypogammaglobulinemia, seroprotection against and hyporesponsiveness to vaccines for hepatitis B and tetanus, BK/JC viruria and human antichimeric antibodies (HACAs). RESULTS: Sequential RTX therapy, initiated at a median of 10 years [interquartile range (IQR) 7.3-14.4], was administered for 1.8 courses/person-year [95% confidence interval (CI) 1.7-2.0] over 2.0 years (95% CI 1.2-3.0). Therapy was associated with postponement of relapses by a median of 3 years in patients with steroid-sensitive disease and 2 years in those with steroid resistance. Relapses were reduced by a mean of 2.0 relapses/person-year (95% CI 1.8-2.2), enabling a reduction in prednisolone dose to 0.04 mg/kg/day (95% CI 0.01-0.11) and withdrawal of additional immunosuppression in 154 (62%) patients. RTX-associated adverse events, occurring at 0.20 events/person-year (95% CI 0.17-0.23), were chiefly comprised of infusion reactions (n = 108) and infections (n = 46); serious adverse events were observed in 10.8% patients, at 0.03 events/person-year (95% CI 0.02-0.05). Hypogammaglobulinemia was observed in 35% of 177 patients and was moderate to severe in 8.5% of cases. Rates of seroprotection at baseline and response following vaccination were lower for hepatitis B [1.9% and 29.4% (n = 52)] than tetanus [65.5% and 34.5% (n = 58)]. BK/JC viruria, without viremia, was observed in 7.3% of 109 cases. A total of 19 of 107 patients (17.8%) had HACAs, which were associated with B cell nondepletion and serum sickness. Age at therapy of <9-10 years was associated with a risk of early relapse, treatment failure and hypogammaglobulinemia following RTX therapy. CONCLUSIONS: Sequential therapy with RTX effectively reduces relapses in patients with difficult-to-treat steroid- and/or CNI-dependent or CNI-refractory nephrotic syndrome. Therapy is associated with high rates of hypogammaglobulinemia and infusion reactions.

Effects of exposure to per- and polyfluoroalkyl substances on vaccine antibodies: A systematic review and meta-analysis based on epidemiological studies.

Vaccines are essential for children to defend against infection. Per- and polyfluoroalkyl substances (PFAS) are emerging contaminants with the characteristics of persistence and bioaccumulation. PFAS exposure can affect the function of the nervous, endocrine, and immune system of animals and humans. We aimed to conduct a systematic review and meta-analysis of the epidemiological studies investigating potential relationships between PFAS exposure and vaccine antibody levels, and assessed whether PFAS would affect vaccine response in healthy children. A literature search was conducted in PubMed, Web of Science, and Scopus databases up to February 2022. We chose studies that measured serum vaccines antibodies and PFAS concentrations of the participants. Essential information, including mean difference of percentage change, regression coefficient, odds ratio, Spearman correlation coefficient, and 95% confidence intervals, were extracted from the selected studies to conduct descriptive analysis and meta-analysis where appropriate. The qualities of these studies were evaluated as well. Finally, nine epidemiological studies about children met our inclusion criteria. A high degree of heterogeneity is observed in terms of breastfeeding time, confounder control, and detection method. Exposure to perfluorooctanoic acid and perfluorohexane sulfonic acid is negatively associated with tetanus antibody level in children without heterogeneity by Cochran's Q test (p = 0.26; p = 0.55), and exposure to perfluorohexane sulfonate is negatively associated with tetanus antibody level but with heterogeneity (p = 0.04). This comprehensive review suggests that PFAS can have adverse health effects on children by hindering the production of vaccine antibodies. There are some consistent and negative associations between children exposure to certain PFAS and tetanus antibody level. The association of the other four vaccines (measles, rubella, mumps, and influenza) with PFAS remains uncertain, because very few studies are available. Further studies are needed to validate the possible associations.

[Shiga toxin and tetanus toxin as a potential biologic weapon]. / Toksyna Shiga oraz toksyna tezcowa jako potencjalna bron.

Toxins produced by the bacteria are of particular interest as potential cargo combat possible for use in a terrorist attack or war. Shiga toxin is usually produced by shiga toxigenic strains of Escherichia coli (STEC - shigatoxigenic Escherichia coli). To infection occurs mostly after eating contaminated beef. Clinical syndromes associated with Shiga toxin diarrhea, hemorrhagic colitis, hemolytic uremic syndrome (HUS - hemolytic uremic syndrome) or thrombotic thrombocytopenic purpura. Treatment is symptomatic. In HUS, in which mortality during an epidemic reaches 20%, extending the kidney injury dialysis may be necessary. Exposure to tetanus toxin produced by Clostridium tetani, resulting in the most generalized tetanus, characterized by increased muscle tension and painful contractions of individual muscle groups. In the treatment beyond symptomatic behavior (among others spasticity medications, anticonvulsants, muscle relaxants) is used tetanus antitoxin and antibiotics (metronidazole choice). A common complication is acute respiratory failure - then it is necessary to implement mechanical ventilation.

Combined Immunosuppression Impairs Immunogenicity to Tetanus and Pertussis Vaccination Among Patients with Inflammatory Bowel Disease.

BACKGROUND: Pertussis epidemics have recently emerged across the United States, prompting broad public health recommendations for adult Tdap vaccination (tetanus, diphtheria, acellular pertussis). The impact of immunosuppressive regimens for inflammatory bowel disease (IBD) on vaccine responses to the Tdap vaccine is not known. METHODS: We performed a prospective controlled trial between April 2011 and March 2012. Adults with IBD were consecutively stratified based on therapeutic regimen into one of 5 groups: A: no IBD therapy or 5-aminosalicylates alone; B: maintenance biologic monotherapy; C: maintenance immunomodulator monotherapy; D: combined biologic and immunomodulator therapy; and E: healthy age-matched controls. Subjects received Tdap, and serum antibody levels against tetanus toxoid, pertussis toxoid, and filamentous hemagglutinin (FHA) were drawn just before and approximately 4 weeks after vaccination. The primary outcome was the booster response rate to each antigen. Secondary outcomes included the differences in pregeometric and postgeometric mean titers. RESULTS: A total of 98 subjects enrolled, and 84 completed the study. Tetanus response rates were 55%, 56%, 40%, 27%, and 63% across groups A to E, respectively. Group D rates were lower than those of group B (P = 0.02). Postvaccination pertussis toxoid responses were 59%, 72%, 47%, 45%, and 75%, while FHA responses were 86%, 72%, 80%, 64%, and 75% across groups A to E, respectively. Prevaccination and postvaccination geometric mean titer differences for FHA were lower in group D than those in group A (P = 0.05). CONCLUSIONS: Antibody responses to tetanus and pertussis vaccination may be affected by therapeutic drug regimen. Patients with IBD should optimally receive Tdap before starting immunomodulators, particularly when used in combination with anti-tumor necrosis factor alpha agents.

Botulinum toxin pretreatment augments the weakening effect of injection with ricin-mAb35 in rabbit extraocular muscle.

PURPOSE: To examine force generation and duration of effect of botulinum toxin pretreatment, followed by injection of ricin-mAb35 in extraocular muscle. METHODS: In normal adult rabbits, one superior rectus muscle was injected with either 5 units botulinum toxin or 1/50 maximally tolerated dose for rats (rMTD) of ricin-mAb35. Additional rabbits were first injected with 5 units botulinum toxin, and after 1, 2, or 4 weeks the same muscle was injected with either 1/10 or 1/50 rMTD ricin-mAb35. In each treatment group, the contralateral muscle was injected with an equal volume of saline. After 12 weeks (1/50 rMTD) or 6 months (1/10 rMTD), the rabbits were euthanized. Both SR muscles were removed and assayed physiologically, using an in vitro apparatus. RESULTS: Twelve weeks after treatment with either botulinum toxin or immunotoxin alone, only ricin-mAb35-treated muscles were weaker than control muscles at tetanic stimulation frequencies. Pretreatment with botulinum toxin prior to injection with immunotoxin, especially at shorter intervals between injections, resulted in significant decreases in twitch and tetanic force generation compared with controls and muscles treated with ricin-mAb35 only or botulinum toxin only. At 6 months, force generation was decreased from control only in muscles treated with the higher dose of ricin-mAb35. Botulinum toxin pretreatment did not augment this effect at 6 months. CONCLUSIONS: Upregulation of postsynaptic nicotinic acetylcholine receptors caused by botulinum toxin pretreatment amplifies the reduction of force generation in extraocular muscle following secondary injection of the immunotoxin ricin-mAb35 within 3 months of treatment.

Movement disorder emergencies.

Movement disorders may present acutely, and failure to recognize and exclude important differential diagnoses can result in significant morbidity or mortality. Unfortunately, much of the literature pertaining to this topic is scattered and not easily accessible. This review aims to address this deficit. Movement disorder emergencies are discussed according to their most likely mode of presentation. Diagnostic considerations and early management principles are reviewed, along with appropriate pathophysiology where relevant.

Sm14 of Schistosoma mansoni in fusion with tetanus toxin fragment C induces immunoprotection against tetanus and schistosomiasis in mice.

We have constructed vectors that permit the expression in Escherichia coli of Schistosoma mansoni fatty acid-binding protein 14 (Sm14) in fusion with the nontoxic, but highly immunogenic, tetanus toxin fragment C (TTFC). The recombinant six-His-tagged proteins were purified by nickel affinity chromatography and used in immunization and challenge assays. Animals inoculated with TTFC in fusion with or coadministered with Sm14 showed high levels of tetanus toxin antibodies, while animals inoculated with Sm14 in fusion with or coadministered with TTFC showed high levels of Sm14 antibodies. In both cases, there were no changes in the type of immune response (Th2) obtained with the fusion proteins compared to those obtained with the nonfused proteins. Mice immunized with the recombinant proteins (TTFC in fusion with or coadministered with Sm14) survived the challenge with tetanus toxin and did not show any symptoms of the disease. Control animals inoculated with either phosphate-buffered saline (PBS) or Sm14 died with severe symptoms of tetanus after 24 h. Mice immunized with the recombinant proteins (Sm14 in fusion with or coadministered with TTFC) showed a 50% reduction in worm burden when they were challenged with S. mansoni cercariae, while control animals inoculated with either PBS or TTFC were not protected. The results show that the expression of other antigens in fusion at the carboxy terminus of TTFC is feasible for the development of a multivalent recombinant vaccine.

Atropine and ODQ antagonize tetanic fade induced by L-arginine in cats

Although it has been demonstrated that nitric oxide (NO) released from sodium nitrite induces tetanic fade in the cat neuromuscular preparations, the effect of L-arginine on tetanic fade and its origin induced by NO have not been studied in these preparations. Furthermore, atropine reduces tetanic fade induced by several cholinergic and anticholinergic drugs in these preparations, whose mechanism is suggested to be mediated by the interaction of acetylcholine with inhibitory presynaptic muscarinic receptors. The present study was conducted in cats to determine the effects of L-arginine alone or after pretreatment with atropine or 1H-[1,2,4]oxadiazole [4,3-a]quinoxalin-1-one (ODQ) on neuromuscular preparations indirectly stimulated at high frequency. Drugs were injected into the middle genicular artery. L-arginine (2 mg/kg) and S-nitroso-N-acetylpenicillamine (SNAP; 16 µg/kg) induced tetanic fade. The Nw-nitro-L-arginine (L-NOARG; 2 mg/kg) alone did not produce any effect, but reduced the tetanic fade induced by L-arginine. D-arginine (2 mg/kg) did not induce changes in tetanic fade. The tetanic fade induced by L-arginine or SNAP was reduced by previous injection of atropine (1.0 µg/kg) or ODQ (15 µg/kg). ODQ alone did not change tetanic fade. The data suggest that the NO-synthase-GC pathway participates in the L-arginine-induced tetanic fade in cat neuromuscular preparations. The tetanic fade induced by L-arginine probably depends on the action of NO at the presynaptic level. NO may stimulate guanylate cyclase increasing acetylcholine release and thereby stimulating presynaptic muscarinic receptors

Metabotropic receptor stimulation coupled to weak tetanus leads to long-term potentiation and a rapid elevation of cytosolic protein kinase C activity.

We have previously shown that short-term potentiation (STP) inducing weak tetanus induces long-term potentiation (LTP) when it is coupled with activation of metabotropic glutamate (mGlu) receptors by trans-(+/-)-1-amino-1,3-cyclopentanedicarboxylic acid (t-ACPD) in rat CA1 slices. In the present study, we examined if this conversion of STP to LTP involves activation of protein kinase C (PKC). Two minutes but not 30 min after coupling, there was a significant increase in the activator-dependent PKC activity in the cytosolic fraction. STP induction or t-ACPD application did not change PKC activity. There was no activity increase in the membrane fraction. STP was also induced by a co-application of gamma-amino-3-hydroxy-5-methyllisoxazole-4-propionic acid (AMPA) and N-methyl-D-aspartic acid (NMDA). Coupling this STP with t-ACPD, however, did not result in an LTP or PKC activity increase, indicating a requirement for synaptic activity. A rapid and transient (< 5 min) increase in cytosolic PKC activity was also seen after the induction of LTP by stronger tetanic stimulation. No LTP tested in the present study was accompanied by activator-independent, persistent increases in PKC activity. STP induction depends on NMDA receptor activation, and the activation of mGlu receptors results in the production of intracellular second messengers. Our results therefore indicate that these separate components may add and bring about PKC activation and LTP.

Trichloroethylene interactions with muscle cells.

The toxic effect of trichlorethylene (TCE) was investigated on isolated muscles prepared from frog and rats. Twitch and tetanic contractions as well as caffeine-induced contractures, were recorded. Trichloroethylene at a concentration of 0.25-4.0 mM depressed the force development of both twitch and tetanic tension in a dose-dependent manner. This effect was not influenced by the type of muscle. As TCE shortened the time to peak of twitch contractions, it may alter the Ca2+ binding kinetics. Subthreshold caffeine concentrations applied after pre-exposure to TCE (1 or 2mM) induced contractures. The same TCE exposure enhanced regular caffeine contractures through increasing the speed of tension development and the absolute force. Exposure to 5 or 10 mM TCE did not affect the first caffeine-induced contracture but enhanced the potency of the second caffeine dose given 15 min after the first. The results suggest that the interaction of TCE with membrane sites is responsible for Ca2+ release for contractile processes.

Diminished activity of protein kinase C in tetanus toxin-treated macrophages and in the spinal cord of mice manifesting generalized tetanus intoxication.

In previous studies, we have demonstrated that tetanus toxin (TT) inhibits macrophage (MO) lysozyme secretion and that the inhibition of secretion was not directly linked to perturbation of cytosolic calcium homeostasis. Because MO secretion in response to phorbol myristate acetate, a stimulus that activates protein kinase C (PKC), was inhibited by TT, we examined whether TT might interfere with PKC activity. We report that MOs treated with TT have diminished PKC activity. Purified TT as well as commercial TT diminished PKC activity, whereas heated TT and supernatant from which TT had been removed had no effect on PKC activity. We further examined PKC activity in homogenates of brain and spinal cord from mice manifesting generalized tetanus. Spinal cord cytosolic PKC activity (pmol/mg of protein per min) was depressed in TT-intoxicated mice (87.3 +/- 25) compared with controls (182.6 +/- 47; P less than .02, n = 7). In contrast, cytosolic protein kinase A activity was similar in control- and TT-treated MOs and mice. These results provide the first evidence that PKC activity is diminished during TT intoxication.

[Investigation of the immunity status towards tetanus of a population of mechanics at the car-factory "Renault" (author's transl)]. / Etude de l'immunité antitétanique d'une population d'ouvriers des usines Renault: influence de différents facteurs dont celle de la contamination des liquides d'usinage par Clostridium tetani.

Tetanus immunity has been studied in a population of mechanics working at the car-factory "Renault". For the study, 283 individuals were divided into 3 groups. The first group consisted of non-vaccined individuals, the second of vaccinated individuals and the third of individuals who had been boostered. The influence of different parameters on tetanus immunity status was considered, i. e. the age of the subjects, the time at which boostering was given, the serotherapy (when it was administered) and the contact with machine lubricating and cooling fluids. Clostridium tetani bacilli and spores were frequently found in aqueous machine fluids. Their presence is a potential hazard for non-vaccinated mechanics coming to contact with the fluids. Tetanus antibody levels in the sera of the tested population were determined in vivo by the toxin neutralization test. The influence on tetanus immunity of the different parameters considered in this paper was subjected to statistical analysis. From the whole population, 27% of the individuals were found to have no protection against tetanus. When age was taken into account, 53% of the individuals over 45 years old and 10% of those under 45 years old were shown to be devoid of tetanus immunity. It could be shown that younger individuals were better protected than older ones, because the formers had been immunized with adsorbed tetanus toxoid and most of the latters with fluid toxoid. Of the individuals in the third group who had received a booster injection within 15 years after primo-vaccination, 98% showed protective tetanus antibody levels in their sera in contrast to 25% when boostering had occurred more than 15 years after primo-vaccination. Contact with machine fluids was found to influence the degree of immunity of only those individuals whose boostering dated back to more than 25 years. Unexpectedly, 3 mechanics seemed to develop immunity after coming into contact with machine fluids. From the results reported here, it is concluded that tetanus immunity in vaccinated individuals should be renewed by a compulsory booster injection given every 5, 10 or, at the minimum, 15 years. Moreover, high-risk populations such as that represented by the mechanics should be immunized or boostered on commencing employment.

Histoautoradiography of central nervous system in rats with generalized tetanus due to 125I-toxin.

Rats were injected i.v. with 125I-tetanus toxin. In autoradiographs of the spinal cord radioactivity was found over the pericarya and in the surroundings of the motoneurones whereas grain density was less over their nuclear region. In addition, pericarya in the lateral horn of the thoracic region and also the bipolar cells of the spinal ganglia contained radioactivity. The central part and the dorsal horns of spinal cord, and the white substance did not show any appreciable radioactivity. Within the medulla oblongata, clusters of large cells representing motor nuclei, as well as some fibre tracts close to them, contained 125I. Forebrain and cerebellum remained free. According to its histoautoradiographic appearance, generalized tetanus can be described best as a combination of multiple local tetani.