Point-Counterpoint: The Hope-Simpson Hypothesis and Its Implications Regarding an Effect of Routine Varicella Vaccination on Herpes Zoster Incidence.

Some 50 years ago, Edgar Hope-Simpson published his hypothesis regarding the interactions between varicella and herpes zoster. As part of this hypothesis, Hope-Simpson postulated that reactivation of varicella zoster virus (VZV) was under immunological control, and that this immunological control could be boosted "endogenously" due to reactivation of latent VZV, and "exogenously" due to exposure to varicella. This hypothesis has important policy implications and remains a source of debate today; namely, does reducing VZV circulation through effective pediatric varicella vaccination programs lead to unintended increases in herpes zoster (HZ) incidence? This article provides 2 very different perspectives on this issue. The first perspective (Rafael Harpaz: Evidence Against an Effect) highlights the empiric experience of the United States, with its population of >300 million, a highly effective national varicella vaccination program lasting >20 years, and with several credible sources of data regarding HZ incidence. The US data have shown an increase in HZ incidence that preceded the availability of varicella vaccination by decades; indeed, HZ rates appear to have plateaued among older adults since varicella vaccination was introduced. Furthermore, HZ rates are not different in states having higher vs lower preschool varicella vaccination rates. The second perspective (Albert J. van Hoek: Evidence for an Effect) cites data that persons with close exposure to children appear to be at lower risk of HZ before universal VZV vaccination, but not so thereafter. Due to historic demographic changes, exogenous boosting could play a role in explaining the observed increase in HZ before varicella vaccination. Thus, it might be difficult to separate declines in exogenous boosting due to demographic changes from those caused by the varicella vaccination program. Additional data will be needed to conclusively rule out an impact of varicella vaccination on HZ.

Estimating infection prevalence using the positive predictive value of self-administered rapid antigen diagnostic tests: An exploration of SARS-CoV-2 surveillance data in the Netherlands from May 2021 to April 2022.

Measuring the severity of the disease of SARS-CoV-2 is complicated by the lack of valid estimations for the prevalence of infection. Self-administered rapid antigen diagnostic tests (Ag-RDTs) were available in the Netherlands since March 2021, requiring confirmation by reverse-transcription polymerase chain reaction (RT-PCR) for positive results. We explored the possibility of utilizing the positive predictive value (PPV) of Ag-RDTs to estimate SARS-CoV-2 prevalence. We used data from all Public Health service testing facilities between 3 May 2021 and 10 April 2022. The PPV was calculated by dividing the number of positive RT-PCR results by the total number of confirmation tests performed, and used to estimate the prevalence and compared with the number of COVID-19 hospital admissions. In total 3,599,894 cases were included. The overall PPV was 91.8% and 88.8% were symptomatic. During our study period, the estimated prevalence ranged between 2-22% in symptomatic individuals and 2-14% in asymptomatic individuals, with a correlation between the estimated prevalence and hospital admissions two weeks later (r = 0.68 (p<0.01) and r = 0.60 (p<0.01) for symptomatic/asymptomatic individuals). The PPV of Ag-RDTs can help estimate changes in SARS-CoV-2 prevalence, especially when used in conjunction with other surveillance systems. However, the used method probably overestimated the true prevalence because of unmonitored differences in test propensity between individuals.

Cost-effectiveness of increased HIV testing among MSM in The Netherlands.

OBJECTIVES: To assess the cost-effectiveness of increased consistent HIV testing among MSM in the Netherlands. METHODS: Among MSM testing at sexually transmitted infection clinics in the Netherlands in 2014-2015, approximately 20% tested consistently every 6 months. We examined four scenarios with increased percentage of MSM testing every 6 months: a small and a moderate increase among all MSM; a small and a moderate increase only among MSM with at least 10 partners in the preceding 6 months. We used an agent-based model to calculate numbers of HIV infections and AIDS cases prevented with increased HIV testing. These numbers were used in an economic model to calculate costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) due to increased testing, over 2018-2027, taking a healthcare payer perspective. RESULTS: A small increase in the percentage testing every 6 months among all MSM resulted in 490 averted HIV infections and an average ICER of &OV0556;27 900/QALY gained. A moderate increase among all MSM, resulted in 1380 averted HIV infections and an average ICER of &OV0556;36 700/QALY gained. Both were not cost-effective, with a &OV0556;20 000 willingness-to-pay threshold. Increasing the percentage testing every 6 months only among MSM with at least 10 partners in the preceding 6 months resulted in less averted HIV infections than increased testing among all MSM, but was on average cost-saving. CONCLUSION: Increased HIV testing can prevent considerable numbers of new HIV infections among MSM, but may be cost-effective only if targeted at high-risk individuals, such as those with many partners.

Zoster vaccination inequalities: A population based cohort study using linked data from the UK Clinical Practice Research Datalink.

OBJECTIVE: To quantify inequalities in zoster vaccine uptake by determining its association with socio-demographic factors: age, gender, ethnicity, immigration status, deprivation (at Lower-layer Super Output Area-level), care home residence and living arrangements. METHOD: This population-based cohort study utilised anonymised primary care electronic health records from England (Clinical Practice Research Datalink) linked to deprivation and hospitalisation data. Data from 35,333 individuals from 277 general practices in England and eligible for zoster vaccination during the two-year period (2013-2015) after vaccine introduction were analysed. Logistic regression was used to obtain adjusted odds ratios (aOR) for the association of socio-demographic factors with zoster vaccine uptake for adults aged 70 years (main target group) and adults aged 79 years (catch-up group). RESULTS: Amongst those eligible for vaccination, 52.4% (n = 18,499) received the vaccine. Socio-demographic factors independently associated with lower zoster vaccine uptake in multivariable analyses were: being older (catch-up group: aged 79 years) aOR = 0.89 (95% confidence interval (CI):0.85-0.93), care home residence (aOR = 0.64 (95%CI: 0.57-0.73)) and living alone (aOR = 0.85 (95%CI: 0.81-0.90)). Uptake decreased with increasing levels of deprivation (p-value for trend<0.0001; aOR most deprived versus least deprived areas = 0.69 (95%CI: 0.64-0.75)). Uptake was also lower amongst those of non-White ethnicities (for example, Black versus White ethnicity: aOR = 0.61 (95%CI: 0.49-0.75)) but was not lower among immigrants after adjusting for ethnicity. Lower uptake was also seen amongst females compared to men in the catch-up group. CONCLUSIONS: Inequalities in zoster vaccine uptake exist in England; with lower uptake among those of non-White ethnicities, and among those living alone, in a care home and in more deprived areas. Tailored interventions to increase uptake in these social groups should assist in realising the aim of mitigating vaccination inequalities. As care home residents are also at higher risk of zoster, improving the uptake of zoster vaccination in this group will also mitigate inequalities in zoster burden.

Identifying social factors amongst older individuals in linked electronic health records: An assessment in a population based study.

Identification and quantification of health inequities amongst specific social groups is a pre-requisite for designing targeted healthcare interventions. This study investigated the recording of social factors in linked electronic health records (EHR) of individuals aged ≥65 years, to assess the potential of these data to identify the social determinants of disease burden and uptake of healthcare interventions. Methodology was developed for ascertaining social factors recorded on or before a pre-specified index date (01/01/2013) using primary care data from Clinical Practice Research Datalink (CPRD) linked to hospitalisation and deprivation data in a cross-sectional study. Social factors included: religion, ethnicity, immigration status, small area-level deprivation, place of residence (including communal establishments such as care homes), marital status and living arrangements (e.g. living alone, cohabitation). Each social factor was examined for: completeness of recording including improvements in completeness by using other linked EHR, timeliness of recording for factors that might change over time and their representativeness (compared with English 2011 Census data when available). Data for 591,037 individuals from 389 practices from England were analysed. The completeness of recording varied from 1.6% for immigration status to ~80% for ethnicity. Linkages provided the deprivation data (available for 82% individuals) and improved completeness of ethnicity recording from 55% to 79% (when hospitalisation data were added). Data for ethnicity, deprivation, living arrangements and care home residence were comparable to the Census data. For time-varying variables such as residence and living alone, ~60% and ~35% respectively of those with available data, had this information recorded within the last 5 years of the index date. This work provides methods to identify social factors in EHR relevant to older individuals and shows that factors such as ethnicity, deprivation, not living alone, cohabitation and care home residence can be ascertained using these data. Applying these methodologies to routinely collected data could improve surveillance programmes and allow assessment of health equity in specific healthcare studies.

Short-term changes in the health state of children with group B meningococcal disease: A prospective, national cohort study.

OBJECTIVES: The short-term impact of childhood invasive meningococcal disease (IMD) on quality-of-life (QoL) remains largely unquantified. This study aimed to quantify QoL loss at the point when illness was at its worst, and assess health state recovery in the months following illness. METHODS: Parents of children aged <16 years with laboratory-confirmed meningococcal group B (MenB) disease in England, with onset dates from November 2012 to May 2013 were asked to complete a short questionnaire, which included EQ-5DY, a version of EQ-5D for 8-15 year-olds. The parents, or child if able, were asked to complete the questionnaires while considering the child's health on the worst day of illness and on the date the questionnaires were completed. RESULTS: The overall response rate was 43% (109/254 children), with no significant differences between respondents and non-respondents. The median time from disease onset to questionnaire completion was 134 days (interquartile range (IQR), 92 to 156 days). After imputation, the median health index was -0.056 (IQR, -0.073 to 0.102) on the worst day of illness, and 1 (IQR 0.866 to 1.000) on the date of questionnaire completion. The respective Visual Analogue Scores (VAS) were 6.5/100.0 (IQR, 0.0 to 20.0) and 95.0/100.0 (IQR, 90.0 to 100.0). The health state of cases with long-term sequelae (n = 41) was significantly worse at follow-up than those who recovered uneventfully (n = 64; 90.0 vs. 98.0; p<0.001), although there was no significant difference on the worst day of illness (5.0 vs. 10.0; p = 0.671). CONCLUSIONS: This work has provided, for the first time, a quantitative estimate of QoL loss at the peak of illness and in the months after MenB disease in children. The magnitude of QoL loss is staggering, with the reported health state being at, or close to, the worst possible outcome imaginable. This study highlights the difficulties in measuring the impact of illness in young children, who often have the highest burden of potentially preventable infectious diseases.

Efficacy of different pneumococcal conjugate vaccine schedules against pneumonia, hospitalisation, and mortality: re-analysis of a randomised trial in the Gambia.

BACKGROUND: Pneumococcal conjugate vaccines (PCV) reduce disease due to Streptococcus pneumoniae. We aimed to determine the efficacy of different PCV schedules in Gambian children. METHODS: We reanalysed data from a randomised placebo-controlled trial. Infants aged 6-51 weeks were allocated to three doses of nine-valent PCV (n=8718) or placebo (n=8719) and followed until age 30 months. We categorised participants to compare: (a) a first dose at age 6 or 10 weeks, (b) intervals of 1 or 2 months between doses, and (c) different intervals between second and third doses. The primary endpoint was first episode of radiologic pneumonia; other endpoints were hospitalisation and mortality. Using the placebo group as the reference population, Poisson regression models were used with follow-up after the first dose to estimate the efficacy of each schedule and from age 6 weeks to estimate the incidence rate difference between schedules. RESULTS: Predicted efficacy in the groups aged 6 weeks (n=2467, 154 events) or 10 weeks (n=2420, 106 events) at first dose against radiologic pneumonia were 32% (95% CI 19-43%) and 33% (95% CI 21-44%), against hospitalisation 14% (95% CI 3-23%) and 17% (95% CI 7-26%), and against mortality 17% (95% CI -3 to 33%) and 16% (95% CI -3 to 32%) respectively. Predicted efficacy in the groups with intervals of 1 month (n=2701, 133 events) or 2 months (n=1351, 58 events) between doses against radiologic pneumonia were 33% (95% CI 20-44%) and 36% (95% CI 24-46%), against hospitalisation 15% (95% CI 5-24%) and 18% (95% CI 8-27%), and against mortality 17% (95% CI -2 to 33%) and 13% (95% CI -8 to 29%) respectively. Efficacy did not differ by interval between second and third doses, nor did the incidence rate difference between schedules. CONCLUSIONS: We found no evidence that efficacy or effectiveness of PCV9 differed when doses were given with modest variability around the scheduled ages or intervals between doses.