Herd Immunity Alters the Conditions for Performing Dose Schedule Comparisons: An Individual-based Model of Pneumococcal Carriage

Yang, Alan; Cai, Francisco Y.; Lipsitch, Marc

doi:10.1101/393108

Cited by 2 publications

(2 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cluster-randomized trials may reveal how reduced-dose schedules affect herd protection. Our direct-effect estimates may inform transmission-dynamic models, helping to illustrate the potential long-term consequences of reduced-dose schedules [7,39,40]. Such evidence can help anticipate the impact of schedule changes on the public health benefits of PCV programs.…”

Section: Discussionmentioning

confidence: 95%

Dose-specific Effectiveness of 7- and 13-Valent Pneumococcal Conjugate Vaccines Against Vaccine-serotype Streptococcus pneumoniae Colonization in Children

Lewnard

Givon-Lavi

Dagan

2019

Clinical Infectious Diseases

View full text Add to dashboard Cite

Background Reduced-dose pneumococcal conjugate vaccine (PCV) schedules are under consideration in countries where children are recommended to receive 3 doses. Whereas PCV-derived protection against vaccine-serotype colonization is responsible for herd effects of vaccination, dose-specific PCV effectiveness against colonization endpoints is not known. We aimed to assess the performance of differing PCV schedules against vaccine-serotype colonization in children. Methods From 2009–2016, we monitored pneumococcal carriage in southern Israel, where children should receive PCV at ages 2 months, 4 months, and 12 months (2 primary [p] +1 booster [b] schedule). We analyzed nasopharyngeal swabs and vaccination histories from 5928 children aged 0–59 months without symptoms of diseases potentially attributable to pneumococci. Matching individuals on age, sex, ethnicity, visit timing, and recent antibiotic receipt, we measured schedule-specific 7-valent PCV (PCV7) and 13-valent PCV (PCV13) effectiveness against vaccine-serotype colonization in a modified case-control framework. We sampled from the distribution of all possible case-control match assignments for statistical analyses. Results Receiving 2 primary-series PCV13 doses conferred 53% (95% confidence interval [CI], 32–67%) protection against PCV13-serotype colonization at ages ≤12 months; 1 primary-series dose was not protective. A 2p+1b PCV13 series conferred 40% (95% CI, 4–67%) and 62% (95% CI, 33–83%) protection against PCV13-serotype colonization at ages 13–24 months and 25–59 months, respectively. Estimates suggested greater PCV13-conferred protection against PCV7-targeted serotypes than the 6 PCV13-only serotypes. As compared to children receiving 2p+1b PCV13 dosing, those receiving 1p+1b and 2p+0b schedules experienced 2.05-fold (95% CI, 1.12–5.00) and 3.33-fold (95% CI, 2.28–4.93) greater odds, respectively, of vaccine-serotype pneumococcal colonization at ages 13–24 months. Conclusions Our results demonstrate real-world effectiveness of 2p+1b PCV dosing against vaccine-serotype colonization. Reduced-dose schedules may confer lower protection against vaccine-serotype carriage during and beyond the first year of life.

show abstract

Section: Discussionmentioning

confidence: 95%

Dose-specific Effectiveness of 7- and 13-Valent Pneumococcal Conjugate Vaccines Against Vaccine-serotype Streptococcus pneumoniae Colonization in Children

Lewnard

Givon-Lavi

Dagan

2019

Clinical Infectious Diseases

View full text Add to dashboard Cite

show abstract

“…Here, we extend an existing and validated individual-based model of P. vivax transmission (10,18) to simulate phase-III clinical trials for radical cure. Individual-based models have been used to design and evaluate clinical trials, both for malaria (19,20) and other infectious diseases (21)(22)(23)(24). To maintain consistency with previous trials, we modeled our phase-III clinical trials after the recent DETECTIVE trials for PQ and TFQ (6)(7)(8).…”

Section: Introductionmentioning

confidence: 99%

How radical is radical cure? Site-specific biases in phase-III clinical trials underestimate the effect of radical cure against Plasmodium vivax hypnozoites

Huber

Koepfli

España

et al. 2021

Preprint

View full text Add to dashboard Cite

Background: Plasmodium vivax relapses caused by reactivating hypnozoites are a major barrier for elimination and control of this form of malaria. Radical cure is a form of therapy capable of addressing this problem. Recent clinical trials of radical cure have yielded efficacy estimates ranging from 65% to 94%, with substantial variation across trial sites. We performed an analysis of simulated trial data using a transmission model to demonstrate that variation in efficacy estimates across trial sites can arise from differences in the conditions under which trials are conducted. Methods and Findings: Our analysis revealed that differences in transmission intensity, heterogeneous exposure, and relapse rate can yield efficacy estimates ranging as wide as 11-82%, despite simulating trial data under the uniform assumption that treatment had a 75% chance of clearing hypnozoites. A longer duration of prophylaxis leads to a greater measured efficacy, particularly at higher transmission intensities, making the comparison of the protection of different radical cure treatment regimens against relapse more challenging. We show that vector control and parasite genotyping offer two potential means to yield more standardized efficacy estimates that better reflect protection against relapse. Conclusions: We predict that site-specific biases are likely to contribute to variation in efficacy estimates both within and across phase-III clinical trials. Future clinical trials can reduce site-specific biases by conducting trials in low-transmission settings where reinfections from mosquito biting are less common, by preventing reinfections using vector control measures, or by identifying and excluding reinfections that occur during follow-up using parasite genotyping methods.

show abstract

Herd Immunity Alters the Conditions for Performing Dose Schedule Comparisons: An Individual-based Model of Pneumococcal Carriage

Cited by 2 publications

References 27 publications

Dose-specific Effectiveness of 7- and 13-Valent Pneumococcal Conjugate Vaccines Against Vaccine-serotype Streptococcus pneumoniae Colonization in Children

Dose-specific Effectiveness of 7- and 13-Valent Pneumococcal Conjugate Vaccines Against Vaccine-serotype Streptococcus pneumoniae Colonization in Children

How radical is radical cure? Site-specific biases in phase-III clinical trials underestimate the effect of radical cure against Plasmodium vivax hypnozoites

Contact Info

Product

Resources

About