Indirect Effects Of Vaccination Research Articles

Cost-effectiveness of the adjuvanted quadrivalent influenza vaccine for older adults in South Korea

ABSTRACT South Korea’s National Immunization Program administers the quadrivalent influenza vaccine (QIV) to manage seasonal influenza, with a particular focus on the elderly. After reviewing the safety and immune response triggered by the adjuvanted QIV (aQIV) in individuals aged 65 and older, the Ministry of Food and Drug Safety in Korea approved its use. However, the extensive impact of aQIV on public health is yet to be fully understood. This study assessed the cost-effectiveness of replacing QIV with aQIV in South Korean adults aged 65 years and older. A dynamic transmission model, calibrated with national influenza data, was applied to compare the influence of aQIV and QIV on older adults and the broader population throughout a single influenza season. This study considered both the direct and indirect effects of vaccination on the elderly. We derived the incremental cost-effectiveness ratios (ICERs) from quality-adjusted life-years (QALYs) and costs incurred, validated through a probabilistic sensitivity analysis with 5,000 simulations. Findings suggest that transitioning to aQIV from QIV in the elderly would be cost-effective, particularly if aQIV’s efficacy reaches or exceeds 56.1%. With an ICER of $29,267/QALY, considerably lower than the $34,998/QALY willingness-to-pay threshold, aQIV presents as a cost-effective option. Thus, implementing aQIV with at least 56.1% efficacy is beneficial from both financial and public health perspectives in mitigating seasonal influenza in South Korea.

The macroeconomic effects of COVID-19 vaccinations in five Asian countries

COVID-19 vaccines were released en masse globally in 2021 and were regarded by policy makers as crucial in dealing with the coronavirus pandemic. An important question is thus to understand the benefits of the vaccines beyond the direct effects of reducing mortality and morbidity. Using available epidemiological evidence on the effectiveness of vaccines we estimate the economic benefits of vaccination in five important Asian economies – India, Indonesia, South Korea, the Philippines and Vietnam – by applying a dynamic multi-country general equilibrium model. This framework captures the direct and indirect effects of vaccination. Our results show net benefits in terms of GDP for all five economies ranging from 0.16% (India) to 1.1% (South Korea); these depend on the degree of vaccination amongst the population. South Korea shows the most significant benefits while other countries experience smaller benefits. Our findings are consistent with other studies estimating the economic benefits of vaccination.

Methods for the estimation of direct and indirect vaccination effects by combining data from individual- and cluster-randomized trials.

Both individually and cluster randomized study designs have been used for vaccine trials to assess the effects of vaccine on reducing the risk of disease or infection. The choice between individually and cluster randomized designs is often driven by the target estimand of interest (eg, direct versus total), statistical power, and, importantly, logistic feasibility. To combat emerging infectious disease threats, especially when the number of events from one single trial may not be adequate to obtain vaccine effect estimates with a desired level of precision, it may be necessary to combine information across multiple trials. In this article, we propose a model formulation to estimate the direct, indirect, total, and overall vaccine effects combining data from trials with two types of study designs: individual-randomization and cluster-randomization, based on a Cox proportional hazards model, where the hazard of infection depends on both vaccine status of the individual as well as the vaccine status of the other individuals in the same cluster. We illustrate the use of the proposed model and assess the potential efficiency gain from combining data from multiple trials, compared to using data from each individual trial alone, through two simulation studies, one of which is designed based on a cholera vaccine trial previously carried out in Matlab, Bangladesh.

Neighborhood-level vaccine impact on COVID-19 infection and hospital admission in Quebec, Canada, during the Delta and early Omicron periods

ObjectiveTo assess the impact of COVID-19 vaccination on COVID-19 infection and hospitalisation at the population-level, and to assess the indirect effects of vaccination in the province of Quebec, Canada. MethodsWe performed a time-stratified, neighborhood-level ecologic study. The exposure was neighborhood-level vaccination (primary series) coverage; outcomes were COVID-19 infection and hospitalisation rates. We used robust Poisson regression to estimate weekly relative rates of infection and hospitalisation versus vaccination. ResultsHigher vaccination coverage was associated with lower COVID-19 infection rates from July 18-December 4 for the year 2021 (Delta period) (RR≈0.46 [0.39; 0.54] – 0.94 [0.83; 1.05], 85–100% vs. 60–74% coverage). From December 5-December 25, this association reversed (RR≈1.28 [1.16; 1.41] – 1.41 [1.31; 1.52]), possibly due to the Omicron variant, social behaviors and accumulation of susceptibles in more vaccinated neighborhoods. Vaccine impact against hospitalisation was maintained throughout (RR≈0.43 [0.29; 0.65] – 0.88 [0.64; 1.22]). Vaccination provided substantial indirect protection (RR≈0.43 [0.34; 0.54] – 0.81 [0.65; 1.03]). ConclusionsThis study confirmed the protective impact of vaccination against severe disease regardless of variant, at the population level. Ecological analyses are a valuable strategy to evaluate vaccination programs. Population-level effects can have substantial effects and should be accounted for in public health and vaccination program planning.

Assessing the COVID-19 vaccination program during the Omicron variant (B.1.1.529) epidemic in early 2022, Tokyo

BackgroundMany countries, including high-income nations, struggled to control epidemic waves caused by the Omicron variant (B.1.1.529), which had an antigenically distinct evolution. Evaluating the direct and indirect effects of vaccination during the Omicron waves is essential to assess virus control policies. The present study assessed the population impacts of a vaccination program during the sixth wave caused by BA.1 and BA.2 from January to May 2022, in Tokyo.MethodsWe analyzed the primary series and booster vaccination coverages and the confirmed cases stratified by vaccination history. We estimated the number of COVID-19 cases that were directly and indirectly prevented by vaccination. To estimate the direct impact, we used a statistical model that compared risks between unvaccinated and vaccinated individuals. A transmission model employing the renewal process was devised to quantify the total effect, given as the sum of the direct and indirect effects.ResultsAssuming that the reporting coverage of cases was 25%, mass vaccination programs, including primary and booster immunizations, directly averted 640,000 COVID-19 cases (95% confidence interval: 624–655). Furthermore, these programs directly and indirectly prevented 8.5 million infections (95% confidence interval: 8.4–8.6). Hypothetical scenarios indicated that we could have expected a 19% or 7% relative reduction in the number of infections, respectively, compared with the observed number of infections, if the booster coverage had been equivalent to that of the second dose or if coverage among people aged 10–49 years had been 10% higher. If the third dose coverage was smaller and comparable to that of the fourth dose, the total number of infections would have increased by 52% compared with the observed number of infections.ConclusionsThe population benefit of vaccination via direct and indirect effects was substantial, with an estimated 65% reduction in the number of SARS-CoV-2 infections compared with counterfactual (without vaccination) in Tokyo during the sixth wave caused by BA.1 and BA.2.

Cost-effectiveness of seasonal influenza vaccination of children in China: a modeling analysis

BackgroundChina has a high burden of influenza-associated illness among children. We aimed to evaluate the cost-effectiveness of introducing government-funded influenza vaccination to children in China (fully-funded policy) compared with the status quo (self-paid policy).MethodsA decision tree model was developed to calculate the economic and health outcomes, from a societal perspective, using national- and provincial-level data. The incremental cost-effectiveness ratio (ICER) [incremental costs per quality-adjusted life year (QALY) gained] was used to compare the fully-funded policy with the self-paid policy under the willingness-to-pay threshold equivalent to national and provincial GDP per capita. Sensitivity analyses were performed and various scenarios were explored based on real-world conditions, including incorporating indirect effect into the analysis.ResultsCompared to the self-paid policy, implementation of a fully-funded policy could prevent 1,444,768 [95% uncertainty range (UR): 1,203,446–1,719,761] symptomatic cases, 92,110 (95% UR: 66,953–122,226) influenza-related hospitalizations, and 6494 (95% UR: 4590–8962) influenza-related death per season. The fully-funded policy was cost-effective nationally (7964 USD per QALY gained) and provincially for 13 of 31 provincial-level administrative divisions (PLADs). The probability of a funded vaccination policy being cost-effective was 56.5% nationally, and the probability in 9 of 31 PLADs was above 75%. The result was most sensitive to the symptomatic influenza rate among children under 5 years [ICER ranging from − 25,612 (cost-saving) to 14,532 USD per QALY gained]. The ICER of the fully-funded policy was substantially lower (becoming cost-saving) if the indirect effects of vaccination were considered.ConclusionsIntroducing a government-funded influenza policy for children is cost-effective in China nationally and in many PLADs. PLADs with high symptomatic influenza rate and influenza-associated mortality would benefit the most from a government-funded influenza vaccination program.

Effectiveness of COVID-19 Vaccination on Transmission: A Systematic Review

Vaccination against infectious disease affords direct protection from vaccine-induced immunity and additional indirect protection for unvaccinated persons. A systematic review was conducted to estimate the indirect effect of COVID-19 vaccination. From PubMed and Embase, 31 studies were included describing the impact of original wild-type COVID-19 vaccines on disease transmission or viral load. Overall, study results showed the effectiveness of COVID-19 vaccination against SARS-CoV-2 transmission (range 16–95%), regardless of vaccine type or number of doses. The effect was apparent, but less pronounced against omicron (range 24–95% for pre-omicron variants versus 16–31% for omicron). Results from viral load studies were supportive, showing SARS-CoV-2 infections in vaccinated individuals had higher Ct values, suggesting lower viral load, compared to infections among the unvaccinated. Based on these findings, well-timed vaccination programs may help reduce SARS-CoV-2 transmission—even in the omicron era. Whether better-matched vaccines can improve effectiveness against transmission in the omicron era needs further study.

Human papillomavirus vaccine effect against human papillomavirus infection in Rwanda: evidence from repeated cross-sectional cervical-cell-based surveys

Rwanda was the first African country to implement national human papillomavirus (HPV) vaccination (against types HPV6, 11, 16, and 18). In 2011, a school-based catch-up programme was initiated to vaccinate girls aged younger than 15 years but it also reached older girls in schools. We aimed to estimate the population-level effect of HPV vaccination on HPV prevalence. Cross-sectional surveys were done between July, 2013, and April, 2014 (baseline), and between March, 2019, and December, 2020 (repeat), in sexually active women aged 17-29 years at health centres in the Nyarugenge District of Kigali, Rwanda. HPV prevalence was assessed in cervical cell samples collected by a health-care worker in PreservCyt solution (Cytyc, Boxbourough, MA, USA) and tested using a general primer (GP5+ or GP6+)-mediated PCR. Adjusted overall, total, and indirect (herd immunity) vaccine effectiveness was computed as the percentage of HPV detection among all women and among unvaccinated women. 1501 participants completed the baseline survey and 1639 completed the repeat survey. HPV vaccine-type prevalence in participants aged 17-29 years decreased from 12% (173 of 1501) in the baseline survey to 5% (89 of 1639) in the repeat survey, with an adjusted overall vaccine effectiveness of 47% (95% CI 31 to 60) and an adjusted indirect vaccine effectiveness of 32% (9 to 49). Among participants aged 17-23 years, who were eligible for catch-up vaccination, the adjusted overall vaccine effectiveness was 52% (35 to 65) and the adjusted indirect vaccine effectiveness was 36% (8 to 55), with important heterogeneity according to education (overall vaccine effectiveness was 68% [51 to 79] in participants with ≥6 years of school completed and 16% [-34 to 47] in those with <6 years) and HIV status (overall vaccine effectiveness was 55% [36 to 69] for HIV-negative participants and 24% [-62 to 64] for HIV-positive participants). In Rwanda, the prevalence of vaccine-targeted HPV types has been significantly decreased by the HPV vaccine programme, most notably in women who were attending school during the catch-up programme in 2011. HPV vaccine coverage and population-level impact is expected to increase in future cohorts who are eligible for routine HPV vaccination at age 12 years. Bill & Melinda Gates Foundation.

Quantification of waning immunity after measles vaccination - evidence from a seroprevalence study.

The aim of this study was to quantify waning rates from seroprevalence data collected in a study of population with a high vaccination coverage and fixed vaccination schedule. Data were collected during the national Immunologic Survey in the Slovak Republic in 2018. The average waning rate after the first dose (age 1.5 - 10 years) is 9.7% per year from the geometric mean titre (GMT) value 2634 mUI/ml. The average waning rate after the second dose (age 10 - 33 years) is significantly lower, 4.8% per year from the lower GMT value 1331 mUI/ml. This decline in antibody levels suggests that vaccine-induced protection may be compromised and results in the increase in the proportion of seronegative/borderline individuals. These outcomes may provide a valuable source for critical assessment of direct and indirect effects of vaccination.

Predicting indirect effects of rotavirus vaccination programs on rotavirus mortality among children in 112 countries

Rotavirus is a leading cause of diarrhea deaths in children, particularly in low-to-middle income countries (LMICs). Licensed rotavirus vaccines provide strong direct protection, but their indirect effect—the protection due to reduced transmission—is not fully understood. We aimed to quantify the population-level effects of rotavirus vaccination and identify factors that drive indirect protection. We used an SIR-like transmission model to estimate the indirect effects of vaccination on rotavirus deaths in 112 LMICs. We performed a regression analysis to identify predictors of indirect effect magnitude (linear regression) and the occurrence of negative indirect effects (logistic regression). Indirect effects contributed to vaccine impacts in all regions, with effect sizes 8-years post-vaccine introduction ranging from 16.9% in the WHO European region to 1.0% in the Western Pacific region. Indirect effect estimates were higher in countries with higher under-5 mortality, higher vaccine coverage, and lower birth rates. Of the 112 countries analyzed, 18 (16%) had at least 1 year with a predicted negative indirect effect. Negative indirect effects were more common in countries with higher birth rate, lower under-5 mortality and lower vaccine coverage. Rotavirus vaccination may have a larger impact than would be expected from direct effects alone, but the impact of these indirect effects is expected to vary by country.

Association between the Seroprevalence of Antibodies against Seasonal Alphacoronaviruses and SARS-CoV-2 Humoral Immune Response, COVID-19 Severity, and Influenza Vaccination

The present study assesses the seroprevalence of antibodies against seasonal human alphacoronaviruses 229E and NL63 among adult patients infected with SARS-CoV-2, and its association with the humoral response to SARS-CoV-2 infection and its severity, and influenza vaccination. A serosurvey was conducted to quantify the presence of IgG antibodies against the nucleocapsid of 229E (anti-229E-N) and NL63 (anti-NL63-N), and anti-SARS-CoV-2 IgG antibodies (against nucleocapsid, receptor-binding domain, S2 domain, envelope, and papain-like protease) for 1313 Polish patients. The seroprevalence of anti-229E-N and anti-NL63 in the studied cohort was 3.3% and 2.4%. Seropositive individuals had a higher prevalence of anti-SARS-CoV-2 IgG antibodies, higher titers of the selected anti-SARS-CoV2 antibodies, and higher odds of an asymptomatic SARS-CoV-2 infection (OR = 2.5 for 229E and OR = 2.7 for NL63). Lastly, the individuals vaccinated against influenza in the 2019/2020 epidemic season had lower odds of seropositivity to 229E (OR = 0.38). The 229E and NL63 seroprevalence was below the expected pre-pandemic levels (up to 10%), likely due to social distancing, increased hygiene, and face masking. The study also suggests that exposure to seasonal alphacoronaviruses may improve humoral responses to SARS-CoV-2 while decreasing the clinical significance of its infection. It also adds to accumulating evidence of the favorable indirect effects of influenza vaccination. However, the findings of the present study are of a correlative nature and thereby do not necessarily imply causation.

Upper age limits for US male human papillomavirus vaccination for oropharyngeal cancer prevention: a microsimulation-based modeling study.

Human papillomavirus (HVP)-positive oropharyngeal cancer is the most common HPV-associated cancer in the United States. The age at acquisition of oral HPV infections that cause oropharyngeal cancer (causal infections) is unknown; consequently, the benefit of vaccination of US men aged 27-45 years remains uncertain. We developed a microsimulation-based, individual-level, state-transition model of oral HPV16 and HPV16-positive oropharyngeal cancer among heterosexual US men aged 15-84 years, calibrated to population-level data. We estimated the benefit of vaccination of men aged 27-45 years for prevention of oropharyngeal cancer, accounting for direct- and indirect effects (ie, herd effects) of male and female vaccination. In the absence of vaccination, most (70%) causal oral HPV16 infections are acquired by age 26 years, and 29% are acquired between ages 27 and 45 years. Among men aged 15-45 years in 2021 (1976-2006 birth cohorts), status quo vaccination of men through age 26 years is estimated to prevent 95% of 153 450 vaccine-preventable cancers. Assuming 100% vaccination in 2021, extending the upper age limit to 30, 35, 40, or 45 years for men aged 27-45 years (1976-1994 cohorts) is estimated to yield small benefits (3.0%, 4.2%, 5.1%, and 5.6% additional cancers prevented, respectively). Importantly, status quo vaccination of men through age 26 years is predicted to result in notable declines in HPV16-positive oropharyngeal cancer incidence in young men by 2035 (51% and 24% declines at ages 40-44 years and 45-49 years, respectively) and noticeable declines (12%) overall by 2045. Most causal oral HPV16 infections in US men are acquired by age 26 years, underscoring limited benefit from vaccination of men aged 27-45 years for prevention of HPV16-positive oropharyngeal cancers.

Direct and indirect vaccination effects on SARS-CoV-2 infection in day-care centres: Evaluating the policy for early vaccination of day-care staff in Germany, 2021.

To mitigate the known high transmission risk in day-care facilities for children aged 0-6years, day-care staff were given priority for SARS-CoV-2 vaccination in Rhineland-Palatinate, Germany, in March 2021. This study assessed direct and indirect effects of early vaccination of day-care staff on SARS-CoV-2 transmission in daycares with the aim to provide a basis for the prioritisation of scarce vaccines in the future. Data came from statutory infectious disease notifications in educational institutions and from in-depth investigations by the district public health authorities. Using interrupted time series analyses, we measured the effect of mRNA-based vaccination of day-care staff on SARS-CoV-2 infections and transmission. Among 566 index cases from day-care centres, the mean number of secondary SARS-CoV-2 infections per index case dropped by -0.60 case per month after March 2021. The proportion of staff among all cases reported from daycares was around 60% in the pre-interruption phase and significantly decreased by 27 percentage points immediately in March 2021 and by further 6 percentage points each month in the post-interruption phase. Early vaccination of day-care staff reduced SARS-CoV-2 cases in the overall day-care setting and thus also protected unvaccinated children. This should inform future decisions on vaccination prioritisation.

2183. Population-based Mortality Rate Trends of Potential Pneumococcal Pneumonia in Brazil from 2006-2019

Abstract Background Pneumococcal Disease is an important public health problem. In 2010, childhood pneumococcal vaccination with the 10-valent conjugate vaccine (PCV-10) was introduced in the Brazilian national immunization program. No public universal program is currently available for older adults; selected populations at risk are eligible to receive pneumococcal vaccine in few public centers across the country. The objective of this study was to assess trends in mortality rate (MR) due to potential pneumococcal pneumonia (PPP) from 2006-2019 in Brazil. Methods Death data were obtained from the Mortality Information System (SIM) and population data from the Brazilian Institute of Geography and Statistics (IBGE). ICD-10 codes included J13-J18. Yearly MR were calculated per 100,000 people. The percentage of change was calculated using average rate in the pre-(2006-2009) and post-PCV10 (2011-2019) vaccine introduction periods. Joinpoint regression was performed to assess changes in rates per 100,000 people and annual percentage changes (APCs) for each line segment and 95% confidence interval were estimated. Results During 2006-2019, 887,304 deaths by PPP occurred in all-age groups. Most cases were reported as unspecific pneumonia (99.8%). Mean MRs decreased in children &amp;lt; 5 years in post-PCV10 period, in contrast to increasing rates in adults ≥ 50 years (Table 1 and Figure 1). Among children less than 18 years, significant decreasing trends in MR by 5.5%, 2.9%, and 1.6% per year were observed in &amp;lt; 1year, 1-4 years, and 5-17 years, respectively, between 2006-2019 (Table 2). Although significantly decreasing trends were observed in 60-64 years and ≥65 years age groups during 2015-2019, the average APC increased by 1.0% (95%CI;0.3%;1.8%) and 1.4% (95%CI;0.5%;2.2%) in the post-PCV-10, respectively (Table 2). Table 1.Mean mortality rates by age groups for potential pneumococcal pneumonia in the pre-vaccination period (2006-2009) and post-vaccination period (2011-2019) , BrazilFigure 1.Mortality rate of pneumonia by age group in parallel with infant vaccination coverage, 2006-2019Table 2.Jointpoint analysis for mortality rate trends of potential pneumococcal pneumonia by age groups, Brazil, 2006-2019 Conclusion In post-PCV10 period, mortality rate of PPP declined mostly for infants. For older adults, the mortality trends have been consistently higher compared to &amp;lt; 18 age groups, being unable to demonstrate indirect effects of childhood vaccination. These findings inform decision makers about needs related to pneumococcal disease prevention and interventions among older adults. Disclosures Cintia I. Parellada, MD, PhD, MSD Brazil: Employee of MSD Brazil, a subsidiary of Merck &amp; Co., Inc.,|MSD Brazil: Stocks/Bonds Ana Luiza Bierrenbach, MD, PhD, Merck &amp; Co., Inc.: Advisor/Consultant Carolina Zampirolli, Msc, Merck &amp; Co., Inc.: Advisor/Consultant|Merck &amp; Co., Inc.: Employee of IQVIA who received funding to execute this study Ariane Abreu, Msc, Merck &amp; Co., Inc.: Advisor/Consultant|Merck &amp; Co., Inc.: Employee of IQVIA who received funding to execute this study Guilherme Julian, Msc, Merck &amp; Co., Inc.: Advisor/Consultant|Merck &amp; Co., Inc.: Employee of IQVIA who received funding to execute this study Thais Moreira, MD, MSc, MSD Brazil: Employee of MSD Brazil, a subsidiary of Merck &amp; Co., Inc.,|MSD Brazil: Stocks/Bonds Licieri Figueiredo, MD, Merck &amp; Co., Inc.: Employee of MSD Brazil, a subsidiary of Merck &amp; Co., Inc.,.

Cost-effectiveness of the 13-valent pneumococcal conjugate vaccine compared to the 10-valent vaccine in children: predictive analysis in the Ecuadorian context

Abstract Objective To evaluate the cost-effectiveness and economic impact of changing childhood vaccination from the 10-valent pneumococcal conjugate vaccine (PCV10) to the 13-valent pneumococcal conjugate vaccine (PCV13) in the context of the Ecuadorian health system. Methods A Markov model was developed based on a hypothetical cohort of children &amp;lt;1 year old with a 2 + 1 vaccination schedule. The model incorporates the most impactful chronic sequelae of invasive pneumococcal disease: bilateral hearing loss, spasticity, neurological deficit, hydrocephalus and epilepsy. At the end of each annual Markov cycle, the children heal with/without sequelae or die. A time horizon of 5 years was considered. The analysis was done from the perspective of the Ministry of Health. Key findings Vaccination with PCV13 is cost-saving (US$ −2940/QALY) in relation to PCV10 considering indirect effects (‘herd effect’) of childhood vaccination over adult population (&amp;gt;65 years). So, PCV13 reduces incident cases of IPD in this adult population by 27.8% compared to PCV10. Simulation of the model in a cohort of 100 000 children &amp;lt;1 year old showed an incidence of 25 cases of IPD with PCV13 versus 40 cases with PCV10, that is, a reduction of 37.5%. A reduction compared to PCV10 in the incidence of pneumonia and meningitis of 30.2 and 57.1%, respectively, was demonstrated. PCV13 decreased mortality by 32% compared to PCV10. Conclusions Vaccination with PCV13 is cost-saving in the Ecuadorian health context and significantly reduces morbidity and mortality in children &amp;lt;5 years and in adults &amp;gt;65 years due to the herd effect. The probabilistic analysis showed consistency in the results.

The indirect effect of mRNA-based COVID-19 vaccination on healthcare workers\u2019 unvaccinated household members

Mass vaccination is effective in reducing SARS-CoV-2 infections among vaccinated individuals. However, it remains unclear how effectively COVID-19 vaccines prevent people from spreading the virus to their close contacts. Using nationwide administrative datasets on SARS-CoV-2 infections, vaccination records, demographics, and unique household IDs, we conducted an observational cohort study to estimate the direct and indirect effectiveness of mRNA-based COVID-19 vaccines in reducing infections among vaccinated healthcare workers and their unvaccinated household members. Our estimates for adults imply indirect effectiveness of 39.1% (95% CI: −7.1% to 65.3%) two weeks and 39.0% (95% CI: 18.9% to 54.0%) eight weeks after the second dose. We find that the indirect effect of mRNA-based COVID-19 vaccines within households is smaller for unvaccinated children than for adults and statistically insignificant. Here, we show that mRNA-based COVID-19 vaccines are associated with a reduction in SARS-CoV-2 infections not only among vaccinated individuals but also among unvaccinated adult household members in a real-world setting.

Estimating the contribution of HIV-infected adults to household pneumococcal transmission in South Africa, 2016-2018: A hidden Markov modelling study.

Human immunodeficiency virus (HIV) infected adults are at a higher risk of pneumococcal colonisation and disease, even while receiving antiretroviral therapy (ART). To help evaluate potential indirect effects of vaccination of HIV-infected adults, we assessed whether HIV-infected adults disproportionately contribute to household transmission of pneumococci. We constructed a hidden Markov model to capture the dynamics of pneumococcal carriage acquisition and clearance observed during a longitudinal household-based nasopharyngeal swabbing study, while accounting for sample misclassifications. Households were followed-up twice weekly for approximately 10 months each year during a three-year study period for nasopharyngeal carriage detection via real-time PCR. We estimated the effect of participant’s age, HIV status, presence of a HIV-infected adult within the household and other covariates on pneumococcal acquisition and clearance probabilities. Of 1,684 individuals enrolled, 279 (16.6%) were younger children (<5 years-old) of whom 4 (1.5%) were HIV-infected and 726 (43.1%) were adults (≥18 years-old) of whom 214 (30.4%) were HIV-infected, most (173, 81.2%) with high CD4+ count. The observed range of pneumococcal carriage prevalence across visits was substantially higher in younger children (56.9–80.5%) than older children (5–17 years-old) (31.7–50.0%) or adults (11.5–23.5%). We estimate that 14.4% (95% Confidence Interval [CI]: 13.7–15.0) of pneumococcal-negative swabs were false negatives. Daily carriage acquisition probabilities among HIV-uninfected younger children were similar in households with and without HIV-infected adults (hazard ratio: 0.95, 95%CI: 0.91–1.01). Longer average carriage duration (11.4 days, 95%CI: 10.2–12.8 vs 6.0 days, 95%CI: 5.6–6.3) and higher median carriage density (622 genome equivalents per millilitre, 95%CI: 507–714 vs 389, 95%CI: 311.1–435.5) were estimated in HIV-infected vs HIV-uninfected adults. The use of ART and antibiotics substantially reduced carriage duration in all age groups, and acquisition rates increased with household size. Although South African HIV-infected adults on ART have longer carriage duration and density than their HIV-uninfected counterparts, they show similar patterns of pneumococcal acquisition and onward transmission.

The Cost-Effectiveness of 13-Valent Pneumococcal Conjugate Vaccine in Seven Chinese Cities.

Objective: This study estimates the cost-effectiveness of vaccination with the 13-valent pneumococcal conjugate vaccine (PCV13) among infants in Beijing, Shanghai, Shenzhen, Chengdu, Karamay, Qingdao, and Suzhou. Methods: A previously published cost-effectiveness model comparing vaccination with PCV13 to no vaccination was localized to the included Chinese cities. A systematic literature review was undertaken to identify age-specific incidence rates for pneumococcal bacteremia, pneumococcal meningitis, pneumonia, and otitis media (AOM). Age-specific direct medical costs of treating the included pneumococcal diseases were taken from the Chinese Health Insurance Association database. The base case analysis evaluated vaccine efficacy using direct effect and indirect effects (DE+ IDE). A subsequent scenario analysis evaluated the model outcomes if only DE was considered. A vaccination rate of 70% was used. The model reported outcomes over a one-year period after it was assumed the vaccine effects had reached a steady state (5–7 years after vaccine introduction) to include the direct and indirect effects of vaccination. Health outcomes were discounted at 5% during the steady-state period. Results: Vaccination with PCV13 was cost-effective in the base case analysis for all included cities with the incremental cost-effectiveness ratio (ICER) ranging from 1145 CNY(Shenzhen) to 15,422 CNY (Qingdao) per quality-adjusted life-year (QALY) gained. PCV13 was the dominant strategy in Shanghai with lower incremental costs and higher incremental QALYs. PCV13 remained cost-effective in the DE-only analysis with all ICERs falling below a cost-effectiveness threshold of three times GDP per capita in each city. Conclusions: Vaccination with PCV13 was a cost-effective strategy in the analyzed cities for both the DE-only and DE + IDE analyses. PCV13 became very cost-effective when a vaccination rate was reached where IDE is observed.

Intracluster correlation coefficients in a large cluster randomized vaccine trial in schools: Transmission and impact of shared characteristics.

Cluster randomized trials (cRCT) to assess vaccine effectiveness incorporate indirect effects of vaccination, helping to inform vaccination policy. To calculate the sample size for a cRCT, an estimate of the intracluster correlation coefficient (ICC) is required. For infectious diseases, shared characteristics and social mixing behaviours may increase susceptibility and exposure, promote transmission and be a source of clustering. We present ICCs from a school-based cRCT assessing the effectiveness of a meningococcal B vaccine (Bexsero, GlaxoSmithKline) on reducing oropharyngeal carriage of Neisseria meningitidis (Nm) in 34,489 adolescents from 237 schools in South Australia in 2017/2018. We also explore the contribution of shared behaviours and characteristics to these ICCs. The ICC for carriage of disease-causing Nm genogroups (primary outcome) pre-vaccination was 0.004 (95% CI: 0.002, 0.007) and for all Nm was 0.007 (95%CI: 0.004, 0.011). Adjustment for social behaviours and personal characteristics reduced the ICC for carriage of disease-causing and all Nm genogroups by 25% (to 0.003) and 43% (to 0.004), respectively. ICCs are also reported for risk factors here, which may be outcomes in future research. Higher ICCs were observed for susceptibility and/or exposure variables related to Nm carriage (having a cold, spending ≥1 night out socializing or kissing ≥1 person in the previous week). In metropolitan areas, nights out socializing was a highly correlated behaviour. By contrast, smoking was a highly correlated behaviour in rural areas. A practical example to inform future cRCT sample size estimates is provided.

Effectiveness of self-financed rotavirus vaccination in Ise City, Japan

ABSTRACT In Japan, the herd immunity effect of rotavirus vaccine has not yet been proven. Here, we conducted active surveillance for hospitalization due to rotavirus acute gastroenteritis (AGE) among children under 5 years of age in pre-rotavirus vaccination years and self-financed rotavirus vaccination years to clarify the rotavirus vaccine effectiveness (VE) in reducing hospitalization rates. A time-series analysis showed that the monthly hospitalization rates observed after vaccine introduction were significantly lower than the forecasted hospitalization rates (p < .001, Mann-Whitney U test). In the third year after vaccine introduction, the hospitalization rate declined despite the low vaccination rate of 27–50% for the two preceding years. We estimated four types of VE, namely direct, indirect, total, and overall. The direct VE was calculated from the relative risk ratio of hospitalizations between vaccinated and unvaccinated children. The indirect VE was defined as the population-level effects of vaccination on children not receiving the vaccine. The total VE was defined as the combination of the direct and indirect VE on children receiving the vaccine. The overall VE was determined by the weighted average of indirect VE on the children not receiving the vaccine and the total VE on the children receiving the vaccine. The direct, indirect, total, and overall VE values were calculated as 82% (95% confidence interval, 52–93), 70% (51–82), 95% (87–98), and 86% (77–91), respectively. The high values of indirect, total, and overall VE indicate that the rotavirus vaccine produces a herd immunity effect.