scholarly journals Post-Exposure Effects of Vaccines on Infectious Diseases

2019 ◽  
Author(s):  
Tara Gallagher ◽  
Marc Lipsitch
Keyword(s):  
Clinical Trials ◽  
Observational Studies ◽  
Case Fatality ◽  
Hepatitis E ◽  
Vaccine Preventable Diseases ◽  
Post Exposure ◽  
Vaccine Trials ◽  
Tick Borne Encephalitis ◽  
Pubmed Database ◽  
Definition Of

AbstractMany available vaccines have demonstrated post-exposure effectiveness, but no published systematic reviews have synthesized these findings. We searched the PubMed database for clinical trials and observational human studies concerning the post-exposure vaccination effects, targeting infections with an FDA-licensed vaccine plus dengue, hepatitis E, malaria, and tick borne encephalitis, which have licensed vaccines outside of the U.S. Studies concerning animal models, serologic testing, and pipeline vaccines were excluded. Eligible studies were evaluated by definition of exposure, and their attempt at distinguishing pre- and post-exposure effects was rated on a scale of 1-4. We screened 4518 articles and ultimately identified 14 clinical trials and 31 observational studies for this review, amounting to 45 eligible articles spanning 7 of the 28 vaccine-preventable diseases. For secondary attack rate, this body of evidence found the following medians for post-exposure vaccination effectiveness: hepatitis A: 85% (IQR: 28; 5 sources), hepatitis B: 85% (IQR: 22; 5 sources), measles: 83% (IQR: 21; 8 sources), varicella: 67% (IQR: 48; 9 sources), smallpox: 45% (IQR: 39; 4 sources), and mumps: 38% (IQR: 7; 2 sources). For case fatality proportions resulting from rabies and smallpox, the vaccine efficacies had medians of 100% (IQR: 0; 6 sources) and 63% (IQR: 50; 8 sources) post-exposure. Although mainly used for preventive measures, many available vaccines can modify or preclude disease if administered after exposure. This post-exposure effectiveness could be important to consider during vaccine trials and while developing new vaccines.

scholarly journals Postexposure Effects of Vaccines on Infectious Diseases

2019 ◽  
Vol 41 (1) ◽  
pp. 13-27 ◽  
Author(s):  
Tara Gallagher ◽  
Marc Lipsitch
Keyword(s):  
Clinical Trials ◽  
Observational Studies ◽  
Case Fatality ◽  
Hepatitis E ◽  
The United States ◽  
Vaccine Preventable Diseases ◽  
Vaccine Trials ◽  
Tick Borne Encephalitis ◽  
Pubmed Database ◽  
Definition Of

Abstract We searched the PubMed database for clinical trials and observational human studies about postexposure vaccination effects, targeting infections with approved vaccines and vaccines licensed outside the United States against dengue, hepatitis E, malaria, and tick-borne encephalitis. Studies of animal models, serologic testing, and pipeline vaccines were excluded. Eligible studies were evaluated by definition of exposure; attempts to distinguish pre- and postexposure effects were rated on a scale of 1 to 4. We screened 4,518 articles and ultimately identified for this review 14 clinical trials and 31 observational studies spanning 7 of the 28 vaccine-preventable diseases. For secondary attack rate, the following medians were found for postexposure vaccination effectiveness: hepatitis A, 85% (interquartile range (IQR), 28; n = 5 sources); hepatitis B, 85% (IQR, 22; n = 5 sources); measles, 83% (IQR, 21; n = 8 sources); varicella, 67% (IQR: 48; n = 9 sources); smallpox, 45% (IQR, 39; n = 4 sources); and mumps, 38% (IQR, 7; n = 2 sources). For case fatality proportions resulting from rabies and smallpox, the median vaccine postexposure efficacies were 100% (IQR, 0; n = 6 sources) and 63% (IQR, 50; n = 8 sources), respectively. Many available vaccines can modify or preclude disease if administered after exposure. This postexposure effectiveness could be important to consider during vaccine trials and while developing new vaccines.

scholarly journals 720. Efficacy of Nifurtimox + Eflornithine in the Treatment of African Trypanosomiasis. Systematic Review

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S459-S459
Author(s):  
Jessica Hidalgo ◽  
Raghavendra Tirupathi ◽  
Juan Fernando Ortiz ◽  
Stephanie P Fabara ◽  
Dinesh Reddy ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Trypanosoma Brucei ◽  
Observational Studies ◽  
Case Fatality ◽  
Patient Discharge ◽  
Tsetse Fly ◽  
Open Label ◽  
Second Stage ◽  
Additional Clinical Trial

Abstract Background Sleeping sickness is an infectious disease transmitted mainly by the Trypanosoma Brucei, with the tsetse fly as a vector. The condition has two stages: The hemolymphatic and the meningo-encephalitic stage. The second stage is caused mainly by the Trypanosoma Brucei Gambiense. The treatment of the second stage has changed from melarsoprol, eflornithine, to now nifurtimox-eflornithine (NECT). This systematic review will focus on the efficacy and the toxicity of the medication. Methods We use PRISMA and MOOSE protocol for this review. On figure 1, we detail the methodology used for the extraction of information from the systematic review. To assess the study's bias, we used Cochrane Collaboration’s tool for risk assessment of the clinical trials and the Robins I tool for the observational studies. Results We collected four clinical trials and two observational studies after an extensive search. Three clinical trials showed that NECT was non-inferior to eflornithine with the following cure rates (NECT VS eflornithine): 1) 96.3% vs. 94.1% ; 2) 90.9% vs. 88.9%; 3) 91.6% vs. 96.5%. An additional clinical trial revealed that the proportion of patient discharge from the hospital was 98.4% (619/629); 95% CI [97.1%; 99.1%]). The two observational studies discussed the pharmacovigilance of the drug and toxicity related to NECT. In one study, patients treated with NECT, 589 (86%) experienced at least one adverse effect (AE) during treatment, and 70 (10.2%) experience serious AE. On average, children experienced fewer AEs than adults. In the other study at least one AE was described in 1043 patients (60.1%), and Serious AE was reported in 19 patients (1.1% of treated), leading to nine deaths (case fatality rate of 0.5%). The major limitations of the studies were the lack of blinding because most of them were open-label. Also, there was heterogenicity in the definition of the outcomes in the observational studies. PRISMA Flow Chart Conclusion NECT is not inferior to eflornithine, and the proportion of patients discharged from the hospital alive showed favorable results. The observational studies revealed a high frequency of AE. However, NECT is more convenient and safe than Eflornithine and Melarsoprol. Disclosures All Authors: No reported disclosures

scholarly journals DEBATE-statistical analysis plans for observational studies

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Bart Hiemstra ◽  
Frederik Keus ◽  
Jørn Wetterslev ◽  
Christian Gluud ◽  
Iwan C. C. van der Horst
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Statistical Analysis ◽  
Observational Study ◽  
Observational Studies ◽  
Data Driven ◽  
Study Power ◽  
Definition Of ◽  
Main Message ◽  
New Item

Abstract Background All clinical research benefits from transparency and validity. Transparency and validity of studies may increase by prospective registration of protocols and by publication of statistical analysis plans (SAPs) before data have been accessed to discern data-driven analyses from pre-planned analyses. Main message Like clinical trials, recommendations for SAPs for observational studies increase the transparency and validity of findings. We appraised the applicability of recently developed guidelines for the content of SAPs for clinical trials to SAPs for observational studies. Of the 32 items recommended for a SAP for a clinical trial, 30 items (94%) were identically applicable to a SAP for our observational study. Power estimations and adjustments for multiplicity are equally important in observational studies and clinical trials as both types of studies usually address multiple hypotheses. Only two clinical trial items (6%) regarding issues of randomisation and definition of adherence to the intervention did not seem applicable to observational studies. We suggest to include one new item specifically applicable to observational studies to be addressed in a SAP, describing how adjustment for possible confounders will be handled in the analyses. Conclusion With only few amendments, the guidelines for SAP of a clinical trial can be applied to a SAP for an observational study. We suggest SAPs should be equally required for observational studies and clinical trials to increase their transparency and validity.

scholarly journals Definition of Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage as an Outcome Event in Clinical Trials and Observational Studies

Stroke ◽  
2010 ◽  
Vol 41 (10) ◽  
pp. 2391-2395 ◽  
Author(s):  
Mervyn D.I. Vergouwen ◽  
Marinus Vermeulen ◽  
Jan van Gijn ◽  
Gabriel J.E. Rinkel ◽  
Eelco F. Wijdicks ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Subarachnoid Hemorrhage ◽  
Cerebral Ischemia ◽  
Observational Studies ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Delayed Cerebral Ischemia ◽  
Definition Of ◽  
Outcome Event

scholarly journals Advances in Hepatitis E Virus Biology and Pathogenesis

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 267
Author(s):  
Shaoli Lin ◽  
Yan-Jin Zhang
Keyword(s):  
Pregnant Women ◽  
Hepatitis E Virus ◽  
Case Fatality ◽  
Hepatitis E ◽  
Host Cells ◽  
High Rate ◽  
Rapid Progression ◽  
Genotype 1 ◽  
Genotype 3 ◽  
Zoonotic Infections

Hepatitis E virus (HEV) is one of the causative agents for liver inflammation across the world. HEV is a positive-sense single-stranded RNA virus. Human HEV strains mainly belong to four major genotypes in the genus Orthohepevirus A, family Hepeviridae. Among the four genotypes, genotype 1 and 2 are obligate human pathogens, and genotype 3 and 4 cause zoonotic infections. HEV infection with genotype 1 and 2 mainly presents as acute and self-limiting hepatitis in young adults. However, HEV infection of pregnant women with genotype 1 strains can be exacerbated to fulminant hepatitis, resulting in a high rate of case fatality. As pregnant women maintain the balance of maternal-fetal tolerance and effective immunity against invading pathogens, HEV infection with genotype 1 might dysregulate the balance and cause the adverse outcome. Furthermore, HEV infection with genotype 3 can be chronic in immunocompromised patients, with rapid progression, which has been a challenge since it was reported years ago. The virus has a complex interaction with the host cells in downregulating antiviral factors and recruiting elements to generate a conducive environment of replication. The virus-cell interactions at an early stage might determine the consequence of the infection. In this review, advances in HEV virology, viral life cycle, viral interference with the immune response, and the pathogenesis in pregnant women are discussed, and perspectives on these aspects are presented.

scholarly journals EULAR points to consider for conducting clinical trials and observational studies in individuals at risk of rheumatoid arthritis

2021 ◽  
pp. annrheumdis-2021-220884
Author(s):  
Kulveer Mankia ◽  
Heidi J Siddle ◽  
Andreas Kerschbaumer ◽  
Deshire Alpizar Rodriguez ◽  
Anca Irinel Catrina ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Risk Factors ◽  
At Risk ◽  
Clinical Trials ◽  
Observational Studies ◽  
Task Force ◽  
Musculoskeletal Symptoms ◽  
Subclinical Inflammation ◽  
Consensus Statements ◽  
Clinical Arthritis

BackgroundDespite growing interest, there is no guidance or consensus on how to conduct clinical trials and observational studies in populations at risk of rheumatoid arthritis (RA).MethodsAn European League Against Rheumatism (EULAR) task force formulated four research questions to be addressed by systematic literature review (SLR). The SLR results informed consensus statements. One overarching principle, 10 points to consider (PTC) and a research agenda were proposed. Task force members rated their level of agreement (1–10) for each PTC.ResultsEpidemiological and demographic characteristics should be measured in all clinical trials and studies in at-risk individuals. Different at-risk populations, identified according to clinical presentation, were defined: asymptomatic, musculoskeletal symptoms without arthritis and early clinical arthritis. Study end-points should include the development of subclinical inflammation on imaging, clinical arthritis, RA and subsequent achievement of arthritis remission. Risk factors should be assessed at baseline and re-evaluated where appropriate; they include genetic markers and autoantibody profiling and additionally clinical symptoms and subclinical inflammation on imaging in those with symptoms and/or clinical arthritis. Trials should address the effect of the intervention on risk factors, as well as progression to clinical arthritis or RA. In patients with early clinical arthritis, pharmacological intervention has the potential to prevent RA development. Participants’ knowledge of their RA risk may inform their decision to participate; information should be provided using an individually tailored approach.ConclusionThese consensus statements provide data-driven guidance for rheumatologists, health professionals and investigators conducting clinical trials and observational studies in individuals at risk of RA.

Can We Trust Observational Studies Using Propensity Scores in the Critical Care Literature? A Systematic Comparison With Randomized Clinical Trials*

2015 ◽  
Vol 43 (9) ◽  
pp. 1870-1879 ◽  
Author(s):  
Georgios D. Kitsios ◽  
Issa J. Dahabreh ◽  
Sean Callahan ◽  
Jessica K. Paulus ◽  
Anthony C. Campagna ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Critical Care ◽  
Observational Studies ◽  
Propensity Scores ◽  
Randomized Clinical Trials ◽  
Systematic Comparison

scholarly journals Analysis of Immunity to Febrile Malaria in Children That Distinguishes Immunity from Lack of Exposure

2009 ◽  
Vol 77 (5) ◽  
pp. 1917-1923 ◽  
Author(s):  
Philip Bejon ◽  
George Warimwe ◽  
Claire L. Mackintosh ◽  
Margaret J. Mackinnon ◽  
Sam M. Kinyanjui ◽  
...  
Keyword(s):  
Cell Surface ◽  
Antibody Response ◽  
Observational Studies ◽  
Asymptomatic Infection ◽  
Bed Nets ◽  
Bed Net ◽  
Red Cell ◽  
Vaccine Trials ◽  
Net Use ◽  
Malaria Episodes

ABSTRACT In studies of immunity to malaria, the absence of febrile malaria is commonly considered evidence of “protection.” However, apparent “protection” may be due to a lack of exposure to infective mosquito bites or due to immunity. We studied a cohort that was given curative antimalarials before monitoring began and documented newly acquired asymptomatic parasitemia and febrile malaria episodes during 3 months of surveillance. With increasing age, there was a shift away from febrile malaria to acquiring asymptomatic parasitemia, with no change in the overall incidence of infection. Antibodies to the infected red cell surface were associated with acquiring asymptomatic infection rather than febrile malaria or remaining uninfected. Bed net use was associated with remaining uninfected rather than acquiring asymptomatic infection or febrile malaria. These observations suggest that most uninfected children were unexposed rather than “immune.” Had they been immune, we would have expected the proportion of uninfected children to rise with age and that the uninfected children would have been distinguished from children with febrile malaria by the protective antibody response. We show that removing the less exposed children from conventional analyses clarifies the effects of immunity, transmission intensity, bed nets, and age. Observational studies and vaccine trials will have increased power if they differentiate between unexposed and immune children.

Systemic Lupus Erythematosus Disease Activity Index 2000 Responder Index-50 Enhances the Ability of SLE Responder Index to Identify Responders in Clinical Trials

2011 ◽  
Vol 38 (11) ◽  
pp. 2395-2399 ◽  
Author(s):  
ZAHI TOUMA ◽  
DAFNA D. GLADMAN ◽  
DOMINIQUE IBAÑEZ ◽  
SHAHRZAD TAGHAVI-ZADEH ◽  
MURRAY B. UROWITZ
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Clinical Trials ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Activity Index ◽  
Disease Activity Index ◽  
Systemic Lupus ◽  
Original Definition ◽  
Definition Of

Objective.To evaluate the performance of the Systemic Lupus Erythematosus (SLE) Responder Index (SRI) when the SLE Disease Activity Index 2000 (SLEDAI-2K) is substituted with SLEDAI-2K Responder Index-50 (SRI-50), a valid and reliable index of disease activity improvement. Also, to determine whether the SRI-50 will enhance the ability of SRI in detecting responders.Methods.Our study was conducted on patients who attended the Lupus Clinic from September 2009 to September 2010. SLEDAI-2K, SRI-50, the British Isles Lupus Assessment Group measure, and the Physician’s Global Assessment were determined initially and at followup. SRI was determined at the followup visit according to its original definition using the SLEDAI-2K score and by substituting SLEDAI-2K with SRI-50.Results.A total of 117 patients with SLEDAI-2K ≥ 4 at baseline were studied. Patients had 1 followup visit over a 3-month period. Twenty-nine percent of patients met the original definition of SRI and 35% of patients met the definition of SRI when SLEDAI-2K was substituted with SRI-50. The use of SRI-50 allowed determination of significant improvement in 7 additional patients. This improvement could not be discerned with the use of SLEDAI-2K as a component of SRI. At followup visits that showed improvement, SRI-50 scores decreased to a greater extent than SLEDAI-2K scores (p < 0.0001).Conclusion.SRI-50 enhances the ability of SRI to identify patients with clinically important improvement in disease activity. SRI-50 was superior to SLEDAI-2K in detecting partial clinical improvement, ≥ 50%, between visits. These properties of the SRI-50 enable it to be used as an independent outcome measure of improvement or as a component of SRI in clinical trials.

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