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Vaccine Feb 2018Most infants are born with immunity to measles through maternal antibodies transferred in pregnancy, which decay over time. However, in measles elimination settings,... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Most infants are born with immunity to measles through maternal antibodies transferred in pregnancy, which decay over time. However, in measles elimination settings, where measles does not circulate endemically and most immunity is from immunization rather than infection, maternal antibody levels are lower. This results in infant immunity that wanes earlier, and a wider susceptibility gap between maternal antibody decay and infant immunization than in non-eliminated settings. We aimed to systematically quantify the extent and duration of protection from measles in infants in settings that have sustained measles elimination.
METHODS
We conducted a systematic review of studies of measles maternal antibody waning in infants in measles elimination settings. We searched MEDLINE, Embase, CINAHL, Scopus, BIOSIS Previews, and Global Health databases for relevant studies. Studies were included if they were set in countries that had eliminated measles for ≥3 years, and if the study cohort included healthy, full-term, unvaccinated infants ≤12 months, born to healthy mothers, and reported a relevant measure of measles maternal antibody in infants. We assessed study quality using the MetaQAT tool.
RESULTS
We identified 4692 unique citations, eight of which met inclusion criteria. One study reported anti-measles antibody in cord blood, six reported antibody in infant sera, and one reported both. Two studies reported that 80 and 100% of infants were protected from measles at birth. One study reported no protection amongst 3-7 month old infants, and another reported limited protection in infants >4 months. The remaining studies reported the proportion of infants with detected antibody, but not the proportion immune.
CONCLUSION
Although limited, these data suggest that in settings that have sustained measles elimination, some infants are susceptible to measles well before the age of routine measles immunization. Setting-specific seroprevalence and vaccine effectiveness studies are required to evaluate this in different jurisdictions.
Topics: Antibodies, Neutralizing; Antibodies, Viral; Enzyme-Linked Immunosorbent Assay; Female; Humans; Immunity, Maternally-Acquired; Immunization; Infant; Infant, Newborn; Male; Measles; Measles Vaccine; Measles virus; Milk, Human; Pregnancy
PubMed: 29398276
DOI: 10.1016/j.vaccine.2018.01.002 -
Clinical Infectious Diseases : An... Dec 2017Naturally occurring botulism is rare, but a large number of cases could result from unintentional or intentional contamination of a commercial food. Despeciated,...
Workgroup Report by the Joint Task Force Involving American Academy of Allergy, Asthma & Immunology (AAAAI); Food Allergy, Anaphylaxis, Dermatology and Drug Allergy (FADDA) (Adverse Reactions to Foods Committee and Adverse Reactions to Drugs, Biologicals, and Latex Committee); and the Centers for...
BACKGROUND
Naturally occurring botulism is rare, but a large number of cases could result from unintentional or intentional contamination of a commercial food. Despeciated, equine-derived, heptavalent botulinum antitoxin (HBAT) is licensed in the United States. Timely treatment reduces morbidity and mortality, but concerns that botulinum antitoxin can induce anaphylaxis exist. We sought to quantify the allergy risk of botulinum antitoxin treatment and the usefulness of skin testing to assess this risk.
METHODS
We conducted a systematic review of (1) allergic reactions to botulinum antitoxin and (2) the predictive value of skin testing (ST) before botulinum antitoxin administration. We searched 5 scientific literature databases, reviewed articles' references, and obtained data from the HBAT manufacturer and from the Centers for Disease Control and Prevention. Anaphylaxis incidence was determined for HBAT and previously employed botulinum antitoxins. We calculated the positive predictive value (PPV) and negative predictive value (NPV) of ST for anaphylaxis related to HBAT and other botulinum antitoxins.
RESULTS
Seven articles were included. Anaphylaxis incidence was 1.64% (5/305 patients) for HBAT and 1.16% (8/687 patients) for all other botulinum antitoxins (relative risk, 1.41 [95% confidence interval, .47-4.27]; P = .5). Observed values for both PPV and NPV for HBAT-ST (33 patients) were 100%. Observed PPVs and NPVs of ST for other botulinum antitoxins (302 patients) were 0-56% and 50%-100%, respectively. There were no reports of fatal anaphylaxis.
CONCLUSIONS
Considering the <2 % rate of anaphylaxis, fatal outcomes, modest predictive value of ST, resource requirements for ST, and the benefits of early treatment, data do not support delaying HBAT administration to perform ST in a mass botulinum toxin exposure. Anaphylactic reactions may occur among 1%-2% of botulinum antitoxin recipients and will require epinephrine and antihistamine treatment and, possibly, intensive care.
Topics: Anaphylaxis; Botulinum Antitoxin; Botulism; Humans; Immunologic Factors; Practice Guidelines as Topic; Skin Tests
PubMed: 29293931
DOI: 10.1093/cid/cix827 -
Clinical Infectious Diseases : An... Dec 2017Botulism is a rare, potentially severe illness, often fatal if not appropriately treated. Data on treatment are sparse. We systematically evaluated the literature on... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Botulism is a rare, potentially severe illness, often fatal if not appropriately treated. Data on treatment are sparse. We systematically evaluated the literature on botulinum antitoxin and other treatments.
METHODS
We conducted a systematic literature review of published articles in PubMed via Medline, Web of Science, Embase, Ovid, and Cumulative Index to Nursing and Allied Health Literature, and included all studies that reported on the clinical course and treatment for foodborne botulism. Articles were reviewed by 2 independent reviewers and independently abstracted for treatment type and toxin exposure. We conducted a meta-analysis on the effect of timing of antitoxin administration, antitoxin type, and toxin exposure type.
RESULTS
We identified 235 articles that met the inclusion criteria, published between 1923 and 2016. Study quality was variable. Few (27%) case series reported sufficient data for inclusion in meta-analysis. Reduced mortality was associated with any antitoxin treatment (odds ratio [OR], 0.16; 95% confidence interval [CI], .09-.30) and antitoxin treatment within 48 hours of illness onset (OR, 0.12; 95% CI, .03-.41). Data did not allow assessment of critical care impact, including ventilator support, on survival. Therapeutic agents other than antitoxin offered no clear benefit. Patient characteristics did not predict poor outcomes. We did not identify an interval beyond which antitoxin was not beneficial.
CONCLUSIONS
Published studies on botulism treatment are relatively sparse and of low quality. Timely administration of antitoxin reduces mortality; despite appropriate treatment with antitoxin, some patients suffer respiratory failure. Prompt antitoxin administration and meticulous intensive care are essential for optimal outcome.
Topics: Botulinum Antitoxin; Botulism; Humans; Immunologic Factors; Treatment Outcome
PubMed: 29293927
DOI: 10.1093/cid/cix815 -
Clinical Infectious Diseases : An... Dec 2017Maternal and fetal outcomes associated with botulism and botulinum antitoxin use during pregnancy and the postpartum period have not been systematically reviewed.
BACKGROUND
Maternal and fetal outcomes associated with botulism and botulinum antitoxin use during pregnancy and the postpartum period have not been systematically reviewed.
METHODS
We searched Global Health, Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, Scopus, and Medline databases from inception to May 2015 for studies published on botulism or botulinum antitoxin use during pregnancy and the postpartum period, as well as the Centers for Disease Control and Prevention National Botulism Surveillance database. Our search identified 4517 citations.
RESULTS
Sixteen cases of botulism during pregnancy (11 in the third trimester) and 1 case during the postpartum period were identified. Ten cases were associated with confirmed or likely foodborne exposure; 2 cases were attributed to wound contamination related to heroin use, and the source of 5 cases was unknown. Eleven women with botulism had progressive neurologic deterioration and respiratory failure, requiring intensive care unit admission. Four women had adverse outcomes, including 2 deaths and 2 women who remained in a persistent vegetative state. No neonatal losses or cases of congenital botulism were reported. Among the 12 cases that reported neonatal data, 6 neonates were born preterm. No adverse maternal or neonatal events were identified as associated with botulinum antitoxin therapy among 11 patients who received it.
CONCLUSIONS
Our review of 17 cases of botulism in pregnant/postpartum women found that more than half required ventilator support, 2 women died, and 6 infants were born prematurely. A high level of clinical suspicion is key for early diagnosis and treatment of botulism. Care of pregnant women or new mothers with botulism can include preparation for possible intubation.
Topics: Botulinum Antitoxin; Botulism; Female; Fetal Diseases; Humans; Immunologic Factors; Pregnancy; Pregnancy Complications, Infectious; Puerperal Infection
PubMed: 29293925
DOI: 10.1093/cid/cix813 -
Clinical Infectious Diseases : An... Dec 2017Botulism manifests with cranial nerve palsies and flaccid paralysis in children and adults. Botulism must be rapidly identified and treated; however, clinical...
BACKGROUND
Botulism manifests with cranial nerve palsies and flaccid paralysis in children and adults. Botulism must be rapidly identified and treated; however, clinical presentation and treatment outcomes of noninfant botulism in children are not well described.
METHODS
We searched 12 databases for peer-reviewed and non-peer-reviewed reports with primary data on botulism in children (persons <18 years of age) or botulinum antitoxin administration to children. Reports underwent title and abstract screening and full text review. For each case, patient demographic, clinical, and outcome data were abstracted.
RESULTS
Of 7065 reports identified, 184 met inclusion criteria and described 360 pediatric botulism cases (79% confirmed, 21% probable) that occurred during 1929-2015 in 34 countries. Fifty-three percent were male; age ranged from 4 months to 17 years (median, 10 years). The most commonly reported signs and symptoms were dysphagia (53%), dysarthria (39%), and generalized weakness (37%). Inpatient length of stay ranged from 1 to 425 days (median, 24 days); 14% of cases required intensive care unit admission; 25% reported mechanical ventilation. Eighty-three (23%) children died. Median interval from illness onset to death was 1 day (range, 0-260 days). Among patients who received antitoxin (n = 193), 23 (12%) reported an adverse event, including rash, fever, serum sickness, and anaphylaxis. Relative risk of death among patients treated with antitoxin compared with patients not treated with antitoxin was 0.24 (95% confidence interval, .14-.40; P < .0001).
CONCLUSIONS
Dysphagia and dysarthria were the most commonly reported cranial nerve symptoms in children with botulism; generalized weakness was described more than paralysis. Children who received antitoxin had better survival; serious adverse events were rare. Most deaths occurred early in the clinical course; therefore, botulism in children should be identified and treated rapidly.
Topics: Adolescent; Botulinum Antitoxin; Botulism; Child; Child, Preschool; Female; Humans; Immunologic Factors; Infant; Male
PubMed: 29293924
DOI: 10.1093/cid/cix812 -
Clinical and Experimental Nephrology Jun 2018The aim of this meta-analysis was to evaluate the efficacy of basiliximab versus antithymocyte globulin for induction therapy in renal allograft. (Comparative Study)
Comparative Study Meta-Analysis Review
OBJECTIVE
The aim of this meta-analysis was to evaluate the efficacy of basiliximab versus antithymocyte globulin for induction therapy in renal allograft.
METHODS
Medline (PubMed), Embase, Ovid, Cochrane, and the Chinese Biomedical Literature databases were searched to identify prospective randomized controlled trials that compared basiliximab with antithymocyte globulin (ATG) for induction therapy in renal transplantation. RevMan 5.1 software and Stat Manager V4.1 software were used for the meta-analysis.
RESULTS
Eight RCTs were included, including a total of 1153 patients. Of these, 547 (47%) had received basiliximab, and 606 (53%) had received ATG. The pooled results revealed that the basiliximab had a lower rate of neoplasm compared with ATG [odds ratio (OR) 0.26; 95% confidence interval (CI) 0.08-0.78; P = 0.02]. There were no significant differences between the two drugs regarding 1-year acute rejection rate (OR 1.32; 95% CI 0.93-1.87; P = 0.13), 1-year graft survival rate (OR 0.73; 95% CI 0.45-1.18; P = 0.20), 1-year patient survival rate (OR 0.52; 95% CI 0.27-1.02; P = 0.06), 1-year infection rate (OR 0.90; 95% CI 0.48-1.68; P = 0.73).
CONCLUSION
Induction therapy of basiliximab has similar short-time effects on the recipients in renal transplantation compared with that of ATG. However, regarding the long-term effect, as represented by the rate of neoplasm, basiliximab has a significant advantage.
Topics: Allografts; Antibodies, Monoclonal; Antilymphocyte Serum; Basiliximab; Graft Rejection; Humans; Immunosuppressive Agents; Kidney Transplantation; Neoplasms; Randomized Controlled Trials as Topic; Recombinant Fusion Proteins
PubMed: 28986715
DOI: 10.1007/s10157-017-1480-z -
Annals of Hematology Dec 2017The first-line formulation of antithymocyte globulin (ATG) remains unknown. We aimed to systematically review evidence to compare the efficacy and safety profiles of... (Comparative Study)
Comparative Study Meta-Analysis Review
The first-line formulation of antithymocyte globulin (ATG) remains unknown. We aimed to systematically review evidence to compare the efficacy and safety profiles of different ATGs. We did a systematic review and meta-analysis of randomized controlled trials (RCTs) and cohort controlled studies comparing horse and rabbit ATG in immunosuppressive therapy of treatment-naïve aplastic anemia. We searched The Cochrane Library, PubMed, EMBASE, ClinicalTrials.gov , and conference proceedings of American Society of Hematology and European Society for Blood and Marrow Transplantation annual meetings. The outcomes were 3-, 6-, and 12-month response; early mortality; relapse; and evolution. We pooled hazard ratios for relapse and odds ratios (ORs) for other outcomes using fixed-effect or random-effect models based on the heterogeneity. This study was registered with PROSPERO, number CRD42016036945. We included 1636 participants from three RCTs and 11 cohort controlled studies. Allocation to horse ATG increased 6-month response events by 86% compared with rabbit ATG. The benefit of horse ATG was mainly driven by increase in studies with non-Asian (OR 95% CI = 2.39 (1.54-3.69), p < 0.0001) and good partial response criterion (OR 95% CI = 2.73 (1.53-4.89), p = 0.0007). The early mortality and evolution were similar between groups. Compared with rabbit ATG, horse ATG had superior remission by 6 months and equivalent safety profiles in patients with treatment-naïve AA. Evidence for further responses beyond 6 to 12 months was limited.
Topics: Anemia, Aplastic; Animals; Antilymphocyte Serum; Female; Horses; Humans; Immunosuppression Therapy; Male; PubMed; Rabbits
PubMed: 28965225
DOI: 10.1007/s00277-017-3136-1 -
Annals of Allergy, Asthma & Immunology... Sep 2017
Review
Topics: Allergens; Bacterial Proteins; Crops, Agricultural; Food Hypersensitivity; Food, Genetically Modified; Humans; Immune Sera; Immunoglobulin E; Plants, Genetically Modified; Risk Assessment; Transgenes; Uncertainty
PubMed: 28890018
DOI: 10.1016/j.anai.2017.07.010 -
Biology of Blood and Marrow... Dec 2017Since 2000, various phase III randomized controlled trials (RCTs) have investigated the efficacy of rabbit antithymocyte globulin (ATG) in patients following allogeneic... (Comparative Study)
Comparative Study Meta-Analysis Review
Since 2000, various phase III randomized controlled trials (RCTs) have investigated the efficacy of rabbit antithymocyte globulin (ATG) in patients following allogeneic stem cell transplantation (allo-SCT). Comparisons of different ATG formulations are lacking, however. Our aim was to synthesize all published efficacy evidence to enable a comparison of all available formulations of rabbit ATG in the allo-SCT setting. We performed a systematic literature review to identify all available phase III RCT evidence. We searched the Cochrane Library, MEDLINE, MEDLINE In-Process, and the website www.ClinicalTrials.gov. In addition, a trial presented at the Annual Meeting of the American Society of Hematology 2016 was added to include the most recent evidence. We identified a total of 6 RCTs, including 2 formulations: anti-T lymphocyte globulin (ATLG; Grafalon, Neovii Biotech, Lexington, MA) and polyclonal globulin immunized with human thymocytes (Thymoglobulin [Thymo]; Genzyme-Sanofi, Cambridge, MA). The evidence was synthesized using a conventional network meta-analysis (NMA). The best treatment for preventing graft-versus-host disease (GVHD) was ATLG, which had a more favorable hazard ratio (HR) compared with standard treatment (chronic GVHD: HR, .42; 95% confidence interval [CI], .31 to .56; acute GVHD grade II-IV: HR, .54; 95% CI, .39 to .73; acute GVHD grade III-IV: HR, .50; 95% CI, .29 to .86), whereas both ATLG and Thymo were at least similarly effective in terms of transplantation-related mortality (TRM) (ATLG: HR, .90; 95% CI, .61 to 1.32; Thymo: HR, .90; 95% CI, .56 to 1.44). Thymo tended to be the better treatment option regarding overall survival (OS) (HR, .86; 95% CI, .59 to 1.26). Our NMA provides the first report of the relative efficacy of all available rabbit ATG formulations in patients undergoing allo-SCT. Until additional data from randomized head-to-head comparisons are available, based on the present analysis, ATLG seems to be the best option to prevent chronic and acute GVHD. Both formulations show similar efficacy in terms of TRM, whereas Thymo appears to be the better treatment option in terms of OS.
Topics: Animals; Antilymphocyte Serum; Graft vs Host Disease; Humans; Network Meta-Analysis; Rabbits; Randomized Controlled Trials as Topic; Stem Cell Transplantation; Survival Rate; Transplantation, Homologous
PubMed: 28864138
DOI: 10.1016/j.bbmt.2017.08.027 -
PloS One 2017B. anthracis anti-toxin agents are approved and included in the Strategic National Stockpile based primarily on animal infection trials. However, in the only anthrax... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
B. anthracis anti-toxin agents are approved and included in the Strategic National Stockpile based primarily on animal infection trials. However, in the only anthrax outbreak an approved anti-toxin agent was administered in, survival did not differ comparing recipients and non-recipients, although recipients appeared sicker.
OBJECTIVE
Employ a systematic review and meta-analysis to investigate preclinical studies supporting anthrax anti-toxin agents.
DATA SOURCE
PubMed, EMBASE, and Scopus.
STUDY ELIGIBILITY
Compared survival with an anti-toxin agent versus control in B. anthracis challenged, antibiotic treated animals.
STUDY METHODS
Examine model and study design and the effect of anti-toxin agents on relative risk of death(95%CI) (RR).
RESULTS
From 9 studies, 29 experiments were analyzed which included 4 species (748 animals) and 5 agents; LFI, AIG, AVP-21D9, Raxibacumab, and ETI-204. Only five experiments were blinded and no experiment included the cardiopulmonary support sick B. anthracis patients receive. Only one agent in a single un-blinded experiment reduced RR significantly [0.45(0.22,0.940]. However, in six studies testing an agent in more than one experiment in the same species, agents had consistent survival effects across experiments [I2 = 0, p≥0.55 in five and I2 = 42%, p = 0.16 in one]. Within each species, agents had effects on the side of benefit; in one study testing AVP-21D9 in mice [0.11(0.01,1.82)] or guinea pigs [0.70(0.48,1.03)]; across eight rabbit studies testing LFI, Raxibacumab, AIG or ETI-204 [0.62(0.45,0.87); I2 = 17.4%, p = 0.29]; and across three monkey studies testing Raxibacumab, AIG or ETI-204 [0.66(0.34,1.27); I2 = 25.3%, p = 0.26]. Across all agents and species, agents decreased RR [0.64(0.52,0.79); I2 = 5.3%, p = 0.39].
LIMITATIONS
Incidence of selective reporting not identifiable.
CONCLUSIONS
Although overall significant, individually anti-toxin agents had weak beneficial effects. Lack of study blinding and relevant clinical therapies further weakened studies. Although difficult, preclinical studies with more robust designs and results are warranted to justify the resources necessary to maintain anti-toxin agents in national stockpiles.
Topics: Animals; Anthrax; Anti-Bacterial Agents; Antigens, Bacterial; Antitoxins; Bacillus anthracis; Disease Models, Animal; Humans; Research Design; Treatment Outcome
PubMed: 28797061
DOI: 10.1371/journal.pone.0182879