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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.

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.

A number of developed countries including Australia have experienced significant pertussis outbreaks in recent years despite consistent high levels of vaccine coverage. Evolutionary changes in Bordetella pertussis carrying variants of the gene encoding pertactin, and the emergence of pertactin-deficient strains (PRN−) in the recent epidemics suggest a possible role of vaccine-driven evolution. In this study, we considered a deterministic 2-strain compartmental model to characterize the relative fitness of PRN− strains and vaccine efficacy against PRN− infection in comparison to the wild-type pertactin-expressing (PRN+) strains. We first showed that the model's equilibrium behavior allows for replacement and co-existence, depending on key parameters related to transmission, vaccine efficacy and durations of immunity. We then fitted the model to epidemiological and pathogen PRN data from the state of New South Wales, Australia. Fitted model parameters showed that the changes in pertussis epidemiology have been governed by a vaccine-escape B. pertussis strain (PRN−) having a basic reproduction number ∼ 1/2 of the wild-type strain which was in circulation prior to April 2009, against which the vaccine was estimated to have substantially reduced efficacy. While not causal, our results suggest that selective pressure from acellular pertussis vaccination is consistent with the changing epidemiology observed in Australia over the analysis period.

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 (R 0 ) that remained >1. Accounting for existing immunity, we estimated that the effective reproduction number (R eff ) <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 R eff 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.

Background: The World Health Organization has targeted rubella virus for elimination regionally. Australia was one of the first countries to implement a nationally funded rubella immunisation program, in 1971, and conducts regular national rubella serosurveillance studies. We aimed to estimate the seroprevalence of rubella-specific IgG antibody in the Australian population by age and sex in 2012–2013, to compare the results with three previous serosurveys conducted in 1996–1999, 2002 and 2007 and to estimate the effective reproduction numbers (Rn). Methods: This study used 2729 serum and plasma specimens, randomly selected from a specimen bank collected in 2012–2013 across Australia. Age groups included in the sample ranged from 1 to 49 years. Sera were tested for rubella-specific IgG-antibody using the Enzygnost anti-rubella IgG enzyme immunoassay and classified as positive, negative or equivocal according to rubella-specific IgG concentrations of >7 IU/ml, <3 IU/ml and 3–7 IU/ml, respectively. Results: The overall proportions seropositive, seronegative and equivocal for rubella-specific IgG were 92.1% (95% CI, 91.0–93.2), 6.7% (95% CI, 5.7–7.7) and 1.2% (95% CI, 0.8–1.6), respectively. The proportion of males seropositive was significantly lower than females in the 30–34 (83.1% vs. 96.8%, p = 0.003), 35–39 (86.1% vs. 96.3%, p = 0.02) and 40–44 (86.1% vs. 95.7%, p = 0.03) year age groups. Rn for rubella in 2012–2013 was estimated to be 0.33 (95% CI 0.28–0.39). Discussion: The 2012–2013 national serosurvey showed levels of rubella-specific IgG seropositivity in the Australian population are relatively high with no evidence of decrease compared to previous serosurveys conducted in 1996–1999, 2002 and 2007. The lower proportion of seropositive males aged 30–44 years likely reflects the initial immunisation program targeting females only. To our knowledge this study represents the longest period of serosurveillance following introduction of a nationally funded rubella

Re-exposure to varicella infection is believed to delay the occurrence of herpes zoster (HZ), which has led to predictions of increased HZ following introduction of varicella vaccination programs. However, there is evidence of rising HZ rates before vaccination was introduced. Here, we explore a potential explanation for this effect through demographic change leading to reductions in varicella exposure and boosting in the context of Australia over the 20th century. To study this hypothesis, we integrated observed changes in Australian birth and age-specific death rates with a varicella transmission model. The model was then calibrated to age-specific pre-vaccination seroprevalence (1997–9) and hospitalization data (1993–2009). Model simulations predicted that declining birth rates led to a 50% reduction in varicella incidence over the 20th century. When combined with the impacts of an aging population, the simulations further suggested that HZ incidence should have increased by 50% over the 20th century. However, we found that after age-standardization, the residual increase in HZ due to reduced boosting was only about 8% over the 20th century. Results were also sensitive to the assumed duration of immunity to HZ and whether multiple HZ episodes were possible. Despite a strong predicted effect of demographic change on varicella incidence, our findings suggest that improved survival is the main contributor to any rise in HZ rates prior to vaccination in Australia. Removing survival effects through age-standardization is recommended when considering epidemiologic or model-based analysis of past trends in HZ.

© 2017 Elsevier Ltd Since licensure of hepatitis A vaccine in Australia in 1994, infection rates have declined to record lows. Cross-sectional serosurveys conducted over this period meanwhile have shown rising population immunity, particularly in young to middle-aged Australians. In this study, we performed a retrospective birth cohort analysis to estimate the contributions of infection, migration and vaccination towards increased levels of age specific hepatitis A seroprevalence in Australia. When aggregated across age, we find that two-thirds of the increase in population seropositivity (67.04%) between 1994 and 2008 was due to vaccination, just under one-third due to migration, with a negligible contribution from infection (<1%). Comparisons with other data sources reflecting vaccine uptake suggest the magnitude of this effect is realistic. We suggest that these results primarily relate to opportunistic vaccination and indicate the level of population immunity achievable through opportunistic programs providing further evidence for policy considerations around universal hepatitis A vaccine recommendations.

Background The 23-valent pneumococcal polysaccharide vaccine (PPV23) has been funded under the Australia National Immunisation Program (NIP) since January 2005 for those aged >65 years and other risk groups. In 2016, PCV13 was accepted by the Pharmaceutical Benefits Advisory Committee (PBAC) as a replacement for a single dose of PPV23 in older Australian adults. Methods A single-cohort deterministic multi-compartment (Markov) model was developed describing the transition of the population between different invasive and non-invasive pneumococcal disease related health states. We applied a healthcare system perspective with costs (Australian dollars, A$) and health effects (measured in quality adjusted life-years, QALYs) attached to model states and discounted at 5% annually. We explored replacement of PPV23 with PCV13 at 65 years as well as other age based vaccination strategies. Parameter uncertainty was explored using deterministic and probabilistic sensitivity analysis. Results In a single cohort, we estimated PCV13 vaccination at the age of 65 years to cost ∼A$11,120,000 and prevent 39 hospitalisations and 6 deaths from invasive pneumococcal disease and 180 hospitalisations and 10 deaths from community acquired pneumonia. The PCV13 program had an incremental cost-effectiveness ratio of ∼A$88,100 per QALY gained when compared to a no-vaccination, whereas PPV23 was ∼A$297,200 per QALY gained. To fall under a cost-effectiveness threshold of A$60,000 per QALY, PCV13 would have to be priced below ∼A$46 per dose. The cost-effectiveness of PCV13 in comparison to PPV23 was ∼A$35,300 per QALY gained. Conclusion In comparison to no-vaccination, we found PCV13 use in those aged 65 years was unlikely to be cost-effective unless the vaccine price was below A$46 or a longer duration of protection can be established. However, we found that in comparison to the PPV23, vaccination with PCV13 was cost-effective. This partly reflects the poor value for money estimated for PPV23 use

Several outbreaks of hepatitis A in men who have sex with men (MSM) were reported in the 1980s and 1990s in Australia and other countries. An effective hepatitis A virus (HAV) vaccine has been available in Australia since 1994 and is recommended for high-risk groups including MSM. No outbreaks of hepatitis A in Australian MSM have been reported since 1996. In this study, we aimed to estimate HAV transmissibility in MSM populations in order to inform targets for vaccine coverage in such populations. We used mathematical models of HAV transmission in a MSM population to estimate the basic reproduction number (R 0) and the probability of an HAV epidemic occurring as a function of the immune proportion. We estimated a plausible range for R 0 of 1·71-3·67 for HAV in MSM and that sustained epidemics cannot occur once the proportion immune to HAV is greater than ~70%. To our knowledge this is the first estimate of R 0 and the critical population immunity threshold for HAV transmission in MSM. As HAV is no longer endemic in Australia or in most other developed countries, vaccination is the only means of maintaining population immunity >70%. Our findings provide impetus to promote HAV vaccination in high-risk groups such as MSM.

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.

Introduction: Vaccine coverage data are typically collected through vaccine registers and retrospective surveys. alternatively, crosssectional serosurveys enable direct estimation of vaccine coverage from antibody prevalence by exploiting correlated seropositivity for multiantigen 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.

Potable reuse is implemented in several countries around the world to augment strained water supplies. This article presents a public health perspective on potable reuse by comparing the critical infrastructure and institutional capacity characteristics of two well-established potable reuse schemes with conventional drinking water schemes in developed nations that have experienced waterborne outbreaks. Analysis of failure events in conventional water systems between 2003 and 2013 showed that despite advances in water treatment technologies, drinking water outbreaks caused by microbial contamination were still frequent in developed countries and can be attributed to failures in infrastructure or institutional practices. Numerous institutional failures linked to ineffective treatment protocols, poor operational practices, and negligence were detected. In contrast, potable reuse schemes that use multiple barriers, online instrumentation, and operational measures were found to address the events that have resulted in waterborne outbreaks in conventional systems in the past decade. Syndromic surveillance has emerged as a tool in outbreak detection and was useful in detecting some outbreaks; increases in emergency department visits and GP consultations being the most common data source, suggesting potential for an increasing role in public health surveillance of waterborne outbreaks. These results highlight desirable characteristics of potable reuse schemes from a public health perspective with potential for guiding policy on surveillance activities.

Introduction: Australia has achieved measles elimination as announced in March 2014 by the WHO Western Pacific Regional Committee, based on several lines of evidence. However, despite strong national evidence for elimination, there remains substantial regional variation in vaccine coverage, has resulted in recent outbreaks and potential for increased frequency in the future. Methods: In this study, we apply a multiple cohort model of measles immunity, stratified by age and local geographic area to predict trends in the measles reproduction number R. In addition, we use branching process models of outbreak risks to predict state-level probabilities of the occurrence of measles outbreaks over the next 20 years. Results: Our results suggest increasing risks of large measles outbreaks over this period, in particular in the states of Queensland and New South Wales. In addition, there is wide variation in predicted R values by smaller geographic areas, although uncertainty in age-specific immunity limits the precision of our results. Discussion: Our predictions align with observed outbreaks in Australian states and suggest our approach to determining future outbreak risks could be applied more widely in elimination or near-elimination settings.

Environmental Impact Assessment (EIA) is a key tool to help ensure sustainable built development in more than 200 countries worldwide. Ecology is frequently a component of EIA and early reviews of Ecological Impact Assessment (EcIA) chapters identified scope for improvement at almost every stage of the EcIA process, regardless of country. However, there have been no reviews of UK EcIA chapters since 2000, despite important changes in biodiversity and planning legislation, policy and guidance. In addition, no UK EcIA chapter reviews have attempted to assign a grade or score to EcIA chapters (as has been done for reviews of US, Finnish and Indian EcIA chapters). Furthermore, no EcIA chapter reviews have attempted to use a scoring system to identify which variables determine EcIA chapter information content, beyond straightforward comparisons of EcIA chapters before and after the introduction of guidelines. A variant of the Biodiversity Assessment Index (BAI) was used to assign scores between zero and one to EcIA chapters based on a series of 47 questions drawn from EU legislation and professional guidance. 112 EcIA chapters for proposed developments that were subsequently granted planning permission in England were assessed. The mean BAI score was less than 0.5, indicating the presence of considerable information gaps in the majority of EcIA chapters. Of 13 predictor variables identified as having the potential to affect EcIA chapter quality, 10 were identified as significantly related to the BAI scores. A backward stepwise Generalized Linear Model identified the use of professional guidance, the ecological consultancy type and the length of the EcIA chapter as having the greatest combined explanatory power. As a result, several recommendations are made to help improve future EcIA chapter content, including formal EcIA chapter review, publicising the professional guidance to consultants, the provision of training and the introduction of an accreditation scheme for con

In Australia, varicella vaccine was universally funded in late 2005 as a single dose at 18 months. A school-based catch-up programme for children aged 10-13 years without a history of infection or vaccination was funded until 2015, when those eligible for universal infant vaccination would have reached the age of high school entry. This study projects the impact of discontinuing catch-up vaccination on varicella and zoster incidence and morbidity using a transmission dynamic model, in comparison with alternative policy options, including two-dose strategies. At current vaccine coverage (83% at 2 years and 90% at 5 years), ceasing the adolescent catch-up programme in 2015 was projected to increase varicella-Associated morbidity between 2035 and 2050 by 39%. Although two-dose infant programmes had the lowest estimated varicella morbidity, the incremental benefit from the second dose fell by 70% if first dose coverage increased from 83% to 95% by age 24 months. Overall zoster morbidity was predicted to rise after vaccination, but differences between strategies were small. Our results suggest that feasibility of one-dose coverage approaching 95% is an important consideration in estimating incremental benefit from a second dose of varicella vaccine.

Over the last decade infant pneumococcal vaccination has been adopted as part of routine immunisation schedules in many developed countries. Although highly successful in many settings such as Australia and the United States, rapid serotype replacement has occurred in some European countries. Recently two pneumococcal conjugate vaccines (PCVs) with extended serotype coverage have been licensed for use, a 10-valent (PHiD-CV) and a 13-valent (PCV-13) vaccine, and offer potential replacements for the existing vaccine (PCV-7) in Australia. To evaluate the cost-effectiveness of PCV programs we developed a static, deterministic state-transition model. The perspective for costs included those to the government and healthcare system. When compared to current practice (PCV-7) both vaccines offered potential benefits, with those estimated for PHiD-CV due primarily to prevention of otitis media and PCV-13 due to a further reduction in invasive disease in Australia. At equivalent total cost to vaccinate an infant, compared to no PCV the base-case cost per QALY saved were estimated at A$64,900 (current practice, PCV-7; 3 + 0), A$50,200 (PHiD-CV; 3 + 1) and A$55,300 (PCV-13; 3 + 0), respectively. However, assumptions regarding herd protection, serotype protection, otitis media efficacy, and vaccination cost changed the relative cost-effectiveness of alternative PCV programs. The high proportion of current invasive disease caused by serotype 19A (as included in PCV-13) may be a decisive factor in determining vaccine policy in Australia.

BACKGROUND: Wide-scale use of antiviral agents in the event of an influenza pandemic is likely to promote the emergence of drug resistance, with potentially deleterious effects for outbreak control. We explored factors promoting resistance within a dynamic infection model, and considered ways in which one or two drugs might be distributed to delay the spread of resistant strains or mitigate their impact. METHODS AND FINDINGS: We have previously developed a novel deterministic model of influenza transmission that simulates treatment and targeted contact prophylaxis, using a limited stockpile of antiviral agents. This model was extended to incorporate subclinical infections, and the emergence of resistant virus strains under the selective pressure imposed by various uses of one or two antiviral agents. For a fixed clinical attack rate, R(0) rises with the proportion of subclinical infections thus reducing the number of infections amenable to treatment or prophylaxis. In consequence, outbreak control is more difficult, but emergence of drug resistance is relatively uncommon. Where an epidemic may be constrained by use of a single antiviral agent, strategies that combine treatment and prophylaxis are most effective at controlling transmission, at the cost of facilitating the spread of resistant viruses. If two drugs are available, using one drug for treatment and the other for prophylaxis is more effective at preventing propagation of mutant strains than either random allocation or drug cycling strategies. Our model is relatively straightforward, and of necessity makes a number of simplifying assumptions. Our results are, however, consistent with the wider body of work in this area and are able to place related research in context while extending the analysis of resistance emergence and optimal drug use within the constraints of a finite drug stockpile. CONCLUSIONS: Combined treatment and prophylaxis represents optimal use of antiviral agents to control transmission, at