Trends in intravenous immunoglobulin use in New South Wales, Australia.

BACKGROUND: Intravenous immunoglobulin (IVIg) is a critical replacement therapy for immunodeficiencies and immunomodulatory treatment for autoimmune and inflammatory diseases. Adequate supply of IVIg is a global issue, necessitating supply restrictions. In Australia, despite strict criteria for use, demand for IVIg has increased over time and exceeds domestic supply. OBJECTIVE: Factors associated with the upward trend in overall IVIg use were examined, including in the number of unique patients, IVIg dosing and treatment frequency and variations by prescribing discipline and disease group. METHODS: De-identified data of IVIg dispensed in the largest Australian state (New South Wales) from 2007 to 2013 were provided by Australian Red Cross Lifeblood. Trends and projections were calculated using log-linear regression of unique patients, treatment episodes and grams of IVIg for overall use and use stratified by discipline and disease group. RESULTS: During the study period, 169 453 treatment episodes were recorded for 12 547 unique patients accounting for 5 827 787 g of IVIg use. Overall, IVIg use increased by 12.0% (11.5-12.6%) per year representing a 97.7% increase (91.6-104%) over the study period. The highest growth was among neurological conditions (16.0% (14.9-17.1%) per year). An increase in the number of unique patients was the primary driver of this growth, augmented by increases in the frequency and average dose per treatment. CONCLUSIONS: Clinically acceptable measures to improve management of IVIg supply are needed including optimising dose, frequency and duration of treatment. Formal evaluation of IVIg versus alternatives, including cost-effectiveness and comparative efficacy, is warranted.

Real-time analysis of hospital length of stay in a mixed SARS-CoV-2 Omicron and Delta epidemic in New South Wales, Australia.

BACKGROUND: The distribution of the duration that clinical cases of COVID-19 occupy hospital beds (the 'length of stay') is a key factor in determining how incident caseloads translate into health system burden. Robust estimation of length of stay in real-time requires the use of survival methods that can account for right-censoring induced by yet unobserved events in patient progression (e.g. discharge, death). In this study, we estimate in real-time the length of stay distributions of hospitalised COVID-19 cases in New South Wales, Australia, comparing estimates between a period where Delta was the dominant variant and a subsequent period where Omicron was dominant. METHODS: Using data on the hospital stays of 19,574 individuals who tested positive to COVID-19 prior to admission, we performed a competing-risk survival analysis of COVID-19 clinical progression. RESULTS: During the mixed Omicron-Delta epidemic, we found that the mean length of stay for individuals who were discharged directly from ward without an ICU stay was, for age groups 0-39, 40-69 and 70 +, respectively, 2.16 (95% CI: 2.12-2.21), 3.93 (95% CI: 3.78-4.07) and 7.61 days (95% CI: 7.31-8.01), compared to 3.60 (95% CI: 3.48-3.81), 5.78 (95% CI: 5.59-5.99) and 12.31 days (95% CI: 11.75-12.95) across the preceding Delta epidemic (1 July 2021-15 December 2021). We also considered data on the stays of individuals within the Hunter New England Local Health District, where it was reported that Omicron was the only circulating variant, and found mean ward-to-discharge length of stays of 2.05 (95% CI: 1.80-2.30), 2.92 (95% CI: 2.50-3.67) and 6.02 days (95% CI: 4.91-7.01) for the same age groups. CONCLUSIONS: Hospital length of stay was substantially reduced across all clinical pathways during a mixed Omicron-Delta epidemic compared to a prior Delta epidemic, contributing to a lessened health system burden despite a greatly increased infection burden. Our results demonstrate the utility of survival analysis in producing real-time estimates of hospital length of stay for assisting in situational assessment and planning of the COVID-19 response.

A Gonococcal Vaccine Has the Potential to Rapidly Reduce the Incidence of Neisseria gonorrhoeae Infection Among Urban Men Who Have Sex With Men.

BACKGROUND: A gonococcal vaccine is urgently needed due to increasing gonorrhea incidence and emerging multidrug-resistant gonococcal strains worldwide. Men who have sex with men (MSM) have among the highest incidences of gonorrhea and may be a key target population for vaccination when available. METHODS: An individual-based, anatomical site-specific mathematical model was used to simulate Neisseria gonorrhoeae transmission in a population of 10 000 MSM. The impact of vaccination on gonorrhea prevalence was assessed. RESULTS: With a gonococcal vaccine of 100% or 50% protective efficacy, gonorrhea prevalence could be reduced by 94% or 62%, respectively, within 2 years if 30% of MSM are vaccinated on presentation for sexually transmitted infection (STI) testing. Elimination of gonorrhea is possible within 8 years with vaccines of ≥ 50% efficacy lasting 2 years, providing a booster vaccination is available every 3 years on average. A vaccine's impact may be reduced if it is not effective at all anatomical sites. CONCLUSIONS: Our study indicates that with a vaccine of modest efficacy and an immunization strategy that targets MSM presenting for STI screening, the prevalence of gonorrhea in this population could be rapidly and substantially reduced.

On realized serial and generation intervals given control measures: The COVID-19 pandemic case.

The SARS-CoV-2 pathogen is currently spreading worldwide and its propensity for presymptomatic and asymptomatic transmission makes it difficult to control. The control measures adopted in several countries aim at isolating individuals once diagnosed, limiting their social interactions and consequently their transmission probability. These interventions, which have a strong impact on the disease dynamics, can affect the inference of the epidemiological quantities. We first present a theoretical explanation of the effect caused by non-pharmaceutical intervention measures on the mean serial and generation intervals. Then, in a simulation study, we vary the assumed efficacy of control measures and quantify the effect on the mean and variance of realized generation and serial intervals. The simulation results show that the realized serial and generation intervals both depend on control measures and their values contract according to the efficacy of the intervention strategies. Interestingly, the mean serial interval differs from the mean generation interval. The deviation between these two values depends on two factors. First, the number of undiagnosed infectious individuals. Second, the relationship between infectiousness, symptom onset and timing of isolation. Similarly, the standard deviations of realized serial and generation intervals do not coincide, with the former shorter than the latter on average. The findings of this study are directly relevant to estimates performed for the current COVID-19 pandemic. In particular, the effective reproduction number is often inferred using both daily incidence data and the generation interval. Failing to account for either contraction or mis-specification by using the serial interval could lead to biased estimates of the effective reproduction number. Consequently, this might affect the choices made by decision makers when deciding which control measures to apply based on the value of the quantity thereof.

Modelling response strategies for controlling gonorrhoea outbreaks in men who have sex with men in Australia.

The ability to treat gonorrhoea with current first-line drugs is threatened by the global spread of extensively drug resistant (XDR) Neisseria gonorrhoeae (NG) strains. In Australia, urban transmission is high among men who have sex with men (MSM) and importation of an XDR NG strain in this population could result in an epidemic that would be difficult and costly to control. An individual-based, anatomical site-specific mathematical model of NG transmission among Australian MSM was developed and used to evaluate the potential for elimination of an imported NG strain under a range of case-based and population-based test-and-treat strategies. When initiated upon detection of the imported strain, these strategies enhance the probability of elimination and reduce the outbreak size compared with current practice (current testing levels and no contact tracing). The most effective strategies combine testing targeted at regular and casual partners with increased rates of population testing. However, even with the most effective strategies, outbreaks can persist for up to 2 years post-detection. Our simulations suggest that local elimination of imported NG strains can be achieved with high probability using combined case-based and population-based test-and-treat strategies. These strategies may be an effective means of preserving current treatments in the event of wider XDR NG emergence.

Impact of a structured older persons health assessment on herpes zoster vaccine uptake in Australian primary care.

Vaccine uptake in adult immunisation programs is often suboptimal. We aimed to assess the impact of the structured older persons health assessment (health assessment) on herpes zoster (zoster) vaccine uptake in Australia. We used national general practice electronic medical records (MedicineInsight) of encounters with patients aged 75-79 years because these patients were age-eligible for both free zoster vaccines and health assessments in the two years following the addition of zoster vaccine to the national immunisation program (Nov 2016-Dec 2018). Due to repeated encounters, we used generalized estimating equations with each patient treated as a clustering variable to analyse the comparison of rates of zoster vaccine administration during encounters where a health assessment was provided versus encounters where the health assessment was not provided. In analyses there were 31,876 patients with a total of 266,204 eligible general practice encounters. Of the 5018 encounters where a health assessment was provided, 592 zoster vaccinations also occurred on the same day (118.0/1000 encounters); for the 261,186 encounters where no health assessment was provided, 9226 zoster vaccinations occurred (35.3/1000 encounters). Zoster vaccine was more likely to be administered during a general practice encounter with a health assessment compared to encounters without one (adjusted odds ratio 2.99; 95% CI: 2.76-3.23). In conclusion, the structured older persons health assessment, which acts as both an incentive and a reminder for healthcare providers to recommend vaccinations in adults improves uptake of zoster vaccine in eligible adults. Such interventions may have a role in improving vaccine uptake among older adults.

Modelling the decline and future of hepatitis A transmission in Australia.

Hepatitis A incidence has declined in most countries through a combination of prevention measures, augmented through the use of a highly effective vaccine. In Australia, the proportion of the population susceptible to hepatitis A infection has declined over time due to high rates of opportunistic vaccination as well as the sustained inflow of seropositive immigrants from high-endemicity countries. These factors have contributed to a rapid decline in incidence. An age-structured hepatitis A transmission model incorporating demographic changes was fitted to seroprevalence and disease notification data and used to project incidence trends and transmission potential for hepatitis A in the general population. Robustness of findings was assessed through worst-case scenarios regarding vaccine uptake, migration and the duration of immunity. The decline in age-specific seroprevalence until the introduction of hepatitis A vaccine in 1994 was well explained through a declining basic reproduction number (R0 ) that remained >1. Accounting for existing immunity, we estimated that the effective reproduction number (Reff ) <1 in the general population of Australia since the early 1990s, declining more rapidly after the introduction of the hepatitis A vaccine. Future projections under a variety of scenarios support Reff remaining <1 with continued low incidence in the general population. In conclusion, our results suggest that sustained endemic transmission in the general Australian population is no longer possible although risks of sporadic outbreaks remain. This suggests potential for local elimination of hepatitis A infection in Australia, provided that elimination criteria can be defined and satisfied in risk groups. The methodology used here to investigate elimination potential can easily be replicated in settings such as in the USA where sequential seroprevalence studies are supported by routine notification data.

Estimating vaccine coverage from serial trivariate serologic data in the presence of waning immunity.

INTRODUCTION: Vaccine coverage data are typically collected through vaccine registers and retrospective surveys. Alternatively, cross-sectional serosurveys enable direct estimation of vaccine coverage from antibody prevalence by exploiting correlated seropositivity for multi-antigen vaccines. Here, we extend previous methods by accounting for temporal antibody decline in estimating vaccine coverage for measles-mumps-rubella vaccine using serial serosurvey data. METHODS: We introduce a Markovian cohort model of antibody waning and boosting applied to dichotomous seropositivity data for measles, mumps, and rubella. Simulation studies are used to test model identifiability and to explore bias induced by previous methods that ignore waning. The cohort model is then fitted to three Australian serosurveys, entailing estimates of vaccine coverage from routine and catch-up vaccination as well as waning rates for each antigen. RESULTS: The simulation results show that the cohort model is identifiable and qualitatively captures the decline in seropositivity observed in older children. When fitted to all three Australian surveys, the estimated seroconversion and waning parameters are similar to estimates based on recent meta-analyses, whereas the coverage estimates appear consistent with previous Australian survey-based estimates. DISCUSSION: We show that previous methods of estimating coverage from serological data can be improved by fitting a cohort model with waning and boosting processes to serial serosurvey data, furthermore yielding estimates of more parameters of interest such as rates of waning. In settings where serial serosurvey data is available, our method could be duplicated or applied to related questions such as coverage in routine two-dose schedules or from other combination vaccines.

Periodicity of varicella-zoster virus in the presence of immune boosting and clinical reinfection with varicella.

BACKGROUND: Clinical reinfection with varicella is normally ignored in mathematical transmission models as it is considered too rare to be important. METHODS: We apply basic bifurcation analysis to a simple mathematical model of varicella-zoster virus (VZV) transmission incorporating reinfection. RESULTS: We demonstrate that under certain conditions this model can exhibit periodic behaviour as opposed to what is observed in VZV models that ignore the possibility of repeat varicella attacks. Periodicity can be induced by a combination of immune boosting and reinfection while the impact of zoster (shingles) recurrence on the onset of periodicity is negligible. CONCLUSIONS: Our results suggest that mathematical models of VZV may benefit from inclusion of repeat varicella.

Evidence compendium and advice on social distancing and other related measures for response to an influenza pandemic.

The role of social distancing measures in mitigating pandemic influenza is not precisely understood. To this end, we have conducted a systematised review, particularly in light of the 2009 pandemic influenza, to better inform the role of social distancing measures against pandemic influenza. Articles were identified from relevant databases and the data were synthesised to provide evidence on the role of school or work place-based interventions, case-based distancing (self-isolation, quarantine), and restriction of mobility and mass gatherings. School closure, whether proactive or reactive, appears to be moderately effective and acceptable in reducing the transmission of influenza and in delaying the peak of an epidemic but is associated with very high secondary costs. Voluntary home isolation and quarantine are also effective and acceptable measures but there is an increased risk of intra-household transmission from index cases to contacts. Work place-related interventions like work closure and home working are also modestly effective and are acceptable, but likely to be economically disruptive. Internal mobility restriction is effective only if prohibitively high (50% of travel) restrictions are applied and mass gatherings occurring within 10 days before the epidemic peak are likely to increase the risk of transmission of influenza.

Review of mathematical models of Neisseria gonorrhoeae vaccine impact: Implications for vaccine development.

An effective prophylactic vaccine for prevention of Neisseria gonorrhoeae infection would have a major impact on sexual and reproductive health worldwide. Interest in developing gonorrhoea vaccines is growing due to the reported high rates of N. gonorrhoeae infections globally, and the threat of antimicrobial resistance. Several gonorrhoea vaccine candidates are currently under evaluation and various mathematical models have been used to assess the potential population-level impact a gonorrhoea vaccine may have once available. Here we review key aspects of gonorrhoea vaccine mathematical modelling studies, including model structures, populations considered, and assumptions used as well as vaccine characteristics and implementation scenarios investigated. The predicted vaccine impact varied between studies, ranging from as little as ∼17 % reduction in N. gonorrhoeae prevalence after 30 years up to 100 % reduction after 5 years. However, all studies predicted that even a partially effective gonorrhoea vaccine could have a substantial impact in reducing N. gonorrhoeae prevalence or incidence, particularly when high coverage is achieved within either important risk groups or the overall sexually active population. As expected, higher vaccine efficacy against acquisition of N. gonorrhoeae and longer duration of protection were linked to greater reductions in infections. A vaccine that alters onward transmission could also substantially reduce infections. Several gaps and research needs have been identified by researchers in the field and via this narrative literature review. For example, future modelling to inform gonorrhoea vaccine development and implementation should consider additional populations that are at high risk of N. gonorrhoeae infection, especially in low- and middle-income settings, as well as the impact of vaccination on the potential adverse sexual and reproductive health outcomes of infection. In addition, more detailed and robust epidemiological, biological, and behavioural data is needed to enable more accurate and robust modelling of gonorrhoea vaccine impact to inform future scientific and public health decision-making.

Modelling the epidemiological impact of maternal respiratory syncytial virus (RSV) vaccination in Australia.

BACKGROUND: Respiratory syncytial virus (RSV) is a leading cause of respiratory illness among infants. A maternal RSV vaccine that protects young infants has recently been approved for registration in Australia. We estimated the population benefits of a future year-round maternal RSV vaccination program in terms of prevented RSV infections and hospitalisations in Australia. METHODS: We described RSV transmission using an age-structured compartmental model calibrated to Australian aggregated monthly RSV-coded hospitalisations in children aged <5 years. We accounted for mother and infant interactions in the model to capture herd effects more realistically. Using the model, we estimated the annual age-specific RSV infections and hospitalisations prevented for a range of assumptions for vaccine efficacy, coverage, and durability to estimate the future impact of year-round maternal RSV vaccination on infants and the wider population. RESULTS: Assuming base case vaccine efficacy, 6 months duration of protection and 70% coverage, RSV hospitalisations were predicted to fall by 60% (from 3.0 to 1.2 per 100 persons) in infants aged <3 months and 40% (from 1.9 to 1.1 per 100 persons) in 3-5-month-olds. These benefits were primarily due to direct protection to infants of vaccinated mothers. This vaccine program was predicted to reduce the population-level RSV infection by about 4%. Coverage and duration assumptions were influential, with higher coverage leading to larger declines in infants <6 months, and increased duration of protection leading to additional declines in infection and hospitalisation risk in older infants aged 6-8 months. CONCLUSIONS: With vaccine uptake similar to that achieved for other maternal vaccines in Australia, a year-round RSV maternal vaccination program is predicted to approximately halve the number of RSV hospitalisations in infants younger than 6 months. There was a small herd effect predicted in the base case but potential for larger benefits if vaccine coverage or the duration of protection exceeds base case assumptions.

The potential impact of a vaccine on Neisseria gonorrhoeae prevalence among heterosexuals living in a high prevalence setting.

BACKGROUND: Treatment of Neisseria gonorrhoeae is under threat with the emergence and spread of antimicrobial resistance. Thus, there is a growing interest in the development of a gonorrhoea vaccine. We used mathematical modelling to assess the impact of a hypothetical vaccine in controlling gonorrhoea among heterosexuals living in a setting of relatively high N. gonorrhoeae prevalence (∼3 %). METHODS: We developed a mathematical model of N. gonorrhoeae transmission among 15-49-year-old heterosexuals, stratified by age and sex, and calibrated to prevalence and sexual behaviour data from South Africa as an example of a high prevalence setting for which we have data available. Using this model, we assessed the potential impact of a vaccine on N. gonorrhoeae prevalence in the entire population. We considered gonorrhoea vaccines having differing impacts on N. gonorrhoeae infection and transmission and offered to different age-groups. RESULTS: The model predicts that N. gonorrhoeae prevalence can be reduced by ∼50 % in 10 years following introduction of a vaccine if annual vaccination uptake is 10 %, vaccine efficacy against acquisition of infection is 25 % and duration of protection is 5 years, with vaccination available to the entire population of 15-49-year-olds. If only 15-24-year-olds are vaccinated, the predicted reduction in prevalence in the entire population is 25 % with equivalent vaccine characteristics and uptake. Although predicted reductions in prevalence for vaccination programmes targeting only high-activity individuals and the entire population are similar over the same period, vaccinating only high-activity individuals is more efficient as the cumulative number of vaccinations needed to reduce prevalence in the entire population by 50 % is ∼3 times lower for this programme. CONCLUSION: Provision of a gonorrhoea vaccine could lead to substantial reductions in N. gonorrhoeae prevalence in a high prevalence heterosexual setting, even with moderate annual vaccination uptake of a vaccine with partial efficacy.

Estimating the excess burden of pertussis disease in Australia within the first year of life, that might have been prevented through timely vaccination.

BACKGROUND: Previous Australian studies have shown that delayed vaccination with each of the three primary doses of diphtheria-tetanus-pertussis-containing vaccines (DTP) is up to 50 % in certain subpopulations. We estimated the excess burden of pertussis that might have been prevented if (i) all primary doses and (ii) each dose was given on time. METHODS: Perinatal, immunization, pertussis notification and death data were probabilistically linked for 1 412 984 infants born in two Australian states in 2000-12. A DTP dose administered >15 days after the recommended age was considered delayed. We used Poisson regression models to compare pertussis notification rates to 1-year of age in infants with ≥1 dose delayed (Aim 1) or any individual dose delayed (Aim 2) versus a propensity weighted counterfactual on-time cohort. RESULTS: Of all infants, 42% had ≥1 delayed DTP dose. We estimated that between 39 to 365 days of age, 85 (95% CI: 61-109) cases per 100 000 infants, could have been prevented if all infants with ≥1 delayed dose had received their three doses within the on-time window. Risk of pertussis was higher in the delayed versus the on-time cohort, so crude rates overestimated the excess burden (110 cases per 100 000 infants (95% CI: 95-125)). The estimated dose-specific excess burden per 100 000 infants was 132 for DTP1, 50 for DTP2 and 19 for DTP3. CONCLUSIONS: We provide robust evidence that improved DTP vaccine timeliness, especially for the first dose, substantially reduces the burden of infant pertussis. Our methodology, using a potential outcomes framework, is applicable to other settings.

Impact of a national immunisation program on herpes zoster incidence in Australia.

OBJECTIVES: To evaluate the impact of the National Herpes Zoster (zoster) Immunisation Program in Australia on zoster incidence. METHODS: Ecological analysis of zoster incidence related to timing of implementation of the national program in vaccine-targeted (70-79 years) and non-targeted age groups (60-69 and 80-89 years) during January 2013-December 2018 was estimated using interrupted time-series analyses. RESULTS: Prior to program commencement (Jan 2013-Oct 2016) in patients aged 60-69, 70-79 and 80-89 years, incidence was mostly stable averaging respectively 7.2, 9.6 and 10.8 per 1000 person-years. In the two years following program commencement, incidence fell steadily in those aged 70-79 years, with an estimated decrease of 2.25 (95% CI: 1.34, 3.17) per 1000 person-years per year, with women having a greater decrease than men (2.83 versus 1.68, p-interaction<0.01). In the two non-vaccine-program-targeted groups there was no evidence of reduction in zoster incidence: 60-69 years, 0.46 (95% CI: -0.46, 1.38) and 80-89 years, 0.11 (95% CI: -1.64, 1.87). CONCLUSIONS: Two years after implementation, an estimated 7000 zoster cases were prevented through the national program. With known waning vaccine efficacy, continued surveillance is needed to ensure these early reductions in incidence are sustained.

Modelled estimates of hospitalisations attributable to respiratory syncytial virus and influenza in Australia, 2009-2017.

BACKGROUND: Respiratory syncytial virus (RSV) and influenza are important causes of disease in children and adults. In Australia, information on the burden of RSV in adults is particularly limited. METHODS: We used time series analysis to estimate respiratory, acute respiratory infection, pneumonia and influenza, and bronchiolitis hospitalisations attributable to RSV and influenza in Australia during 2009 through 2017. RSV and influenza-coded hospitalisations in <5-year-olds were used as proxies for relative weekly viral activity. RESULTS: From 2009 to 2017, the estimated all-age average annual rates of respiratory hospitalisations attributable to RSV and seasonal influenza (excluding 2009) were 54.8 (95% confidence interval [CI]: 20.1, 88.8) and 87.8 (95% CI: 74.5, 97.7) per 100,000, respectively. The highest estimated average annual RSV-attributable respiratory hospitalisation rate per 100,000 was 464.2 (95% CI: 285.9, 641.2) in <5-year-olds. For seasonal influenza, it was 521.6 (95% CI: 420.9, 600.0) in persons aged ≥75 years. In ≥75-year-olds, modelled estimates were approximately eight and two times the coded estimates for RSV and seasonal influenza, respectively. CONCLUSIONS: RSV and influenza are major causes of hospitalisation in young children and older adults in Australia, with morbidity underestimated by hospital diagnosis codes.

Estimating pertussis incidence in general practice using a large Australian primary care database.

BACKGROUND: While pertussis is notifiable in most countries, notifications typically underestimate the true pertussis burden. We explored the incidence of pertussis in general practice in Australia. METHODS: Using MedicineInsight, a large longitudinal electronic medical record database of general practice (primary care) encounters which includes >1.5 million patients, we first defined a cohort of active patients and then used free-text search algorithms to identify patients with pertussis-related encounters. We defined and identified pertussis-related encounters in four patient categories: pertussis-associated (category 1), potential pertussis (category 2), epidemiologically-linked pertussis (category 3), and symptoms consistent with pertussis (category 4). Incident pertussis-related encounter rates per 100,000 active patients were calculated from Jan 2008 to Aug 2015. RESULTS: Estimated mean annual pertussis incidence increased as definitions were expanded, from 94.3 (category 1 patients only) to 148.8 (categories 1+2+3 patients combined) per 100,000 active patients per year. Monthly time-series corresponding to the first three categories were highly correlated (Pearson's r > 90% for each pair), but each was poorly correlated with category 4. For categories 1+2+3, the highest incidence was among 0-4 and 5-9 year olds. Incidence was 30% higher in females than males (i.e. 184.5 vs 139.8 per 100,00 active patients for categories 1-3 patients combined). Pertussis-associated incidence (category 1) was similar to national pertussis notification rates. Categories 2 and 3 added 25% and 33%, respectively, on average relative to category 1 incidence. The estimated incidence from categories 1+2+3 together were on average 64% higher than national pertussis notification rates. CONCLUSION: We provide comprehensive estimates of pertussis-related incidence in general practice (primary care), well in excess of notified pertussis incidence in Australia. This highlights the utility of MedicineInsight data in providing a greater understanding of the burden of medically-attended pertussis infections.

Effectiveness of the live-attenuated herpes zoster vaccine 2 years after its introduction in Australia.

BACKGROUND: The Australian National Herpes Zoster Immunisation Program commenced in November 2016 for people aged 70-79 years old in Australia but vaccine effectiveness (VE) in this setting has not previously been assessed. METHODS: We extracted records from two cohorts of patients aged 70-79 years in 2017 and 2018 respectively who were regular attenders in a nationwide general practice dataset, MedicineInsight. Cox proportional hazards models were used to estimate VE. Models were adjusted for potential confounders including age, sex, and other covariates. Analyses were also stratified by sex, presence of comorbid conditions and number of general practitioner (GP) visits in the previous year. RESULTS: The 2017 cohort included 40,275 regular attenders and the 2018 cohort 41,735. Both cohorts had a mean age of 73.9 years and 52% were women. In 2017, among vaccinated people, over 9,688 person-years of follow-up, 35 cases of zoster were diagnosed giving an incidence of 3.6 per 1000 person-years compared to 8.7 per 1000 person-years (264 cases/30,317 person-years) among unvaccinated people. For 2018, among vaccinated people there were 66 incident zoster cases over 16,716 person-years giving an incidence of 3.9 per 1000 person-years compared to 6.3 per 1000 person-years (156 cases/24,782 person-years) among the unvaccinated. Overall, in the first year of the program, when the average time since vaccination was about 8 months, VE was 63.5% (95% CI: 47.5, 74.6) but this fell to 48.2% (95% CI: 30.0, 61.7) in the second year when the average time since vaccination was about 18 months. We found no difference in VE across age, sex, presence of comorbid conditions, and prior GP visit frequency (P-interaction > 0.05). CONCLUSIONS: VE was consistent with that estimated in other countries and international settings. However, our findings suggest waning effectiveness after the first year of the program. Further program evaluation is necessary.

Global production capacity of seasonal and pandemic influenza vaccines in 2019.

Vaccines will be an important element in mitigating the impact of an influenza pandemic. While research towards developing universal influenza vaccines is ongoing, the current strategy for vaccine supply in a pandemic relies on seasonal influenza vaccine production to be switched over to pandemic vaccines. Understanding how much vaccine could be produced, in which regions of the world and in what timeframe is critical to informing influenza pandemic preparedness. Through the Global Action Plan for Influenza Vaccines, 2006-2016, WHO promoted an increase in vaccine production capacity and monitors the landscape through periodically surveying influenza vaccine manufacturers. This study compares global capacity for production of influenza vaccines in 2019 with estimates from previous surveys; provides an overview of countries with established production facilities; presents vaccine production by type and manufacturing process; and discusses limitations to these estimates. Results of the current survey show that estimated annual seasonal influenza vaccine production capacity changed little since 2015 increasing from 1.47 billion to 1.48 billion doses with potential maximum annual influenza pandemic vaccine production capacity increasing from 6.37 billion to 8.31 billion doses. However, this figure should be interpreted with caution as it presents a best-case scenario with several assumptions which may impact supply. Further, pandemic vaccines would not be immediately available and could take four to six months for first supplies with several more months needed to reach maximum capacity. A moderate-case scenario is also presented of 4.15 billion doses of pandemic vaccine in 12 months. It is important to note that two doses of pandemic vaccine are likely to be required to elicit an adequate immune response. Continued efforts are needed to ensure the sustainability of this production and to conduct research for vaccines that are faster to produce and more broadly protective taking into account lessons learned from COVID-19 vaccine development.

Understanding COVID-19 dynamics and the effects of interventions in the Philippines: A mathematical modelling study.

BACKGROUND: COVID-19 initially caused less severe outbreaks in many low- and middle-income countries (LMIC) compared with many high-income countries, possibly because of differing demographics, socioeconomics, surveillance, and policy responses. Here, we investigate the role of multiple factors on COVID-19 dynamics in the Philippines, a LMIC that has had a relatively severe COVID-19 outbreak. METHODS: We applied an age-structured compartmental model that incorporated time-varying mobility, testing, and personal protective behaviors (through a "Minimum Health Standards" policy, MHS) to represent the first wave of the Philippines COVID-19 epidemic nationally and for three highly affected regions (Calabarzon, Central Visayas, and the National Capital Region). We estimated effects of control measures, key epidemiological parameters, and interventions. FINDINGS: Population age structure, contact rates, mobility, testing, and MHS were sufficient to explain the Philippines epidemic based on the good fit between modelled and reported cases, hospitalisations, and deaths. The model indicated that MHS reduced the probability of transmission per contact by 13-27%. The February 2021 case detection rate was estimated at ~8%, population recovered at ~9%, and scenario projections indicated high sensitivity to MHS adherence. INTERPRETATION: COVID-19 dynamics in the Philippines are driven by age, contact structure, mobility, and MHS adherence. Continued compliance with low-cost MHS should help the Philippines control the epidemic until vaccines are widely distributed, but disease resurgence may be occurring due to a combination of low population immunity and detection rates and new variants of concern.