Respiratory Syncytial Virus Vaccination during Pregnancy and Effects in Infants.

BACKGROUND: Respiratory syncytial virus (RSV) is the dominant cause of severe lower respiratory tract infection in infants, with the most severe cases concentrated among younger infants. METHODS: Healthy pregnant women, at 28 weeks 0 days through 36 weeks 0 days of gestation, with an expected delivery date near the start of the RSV season, were randomly assigned in an overall ratio of approximately 2:1 to receive a single intramuscular dose of RSV fusion (F) protein nanoparticle vaccine or placebo. Infants were followed for 180 days to assess outcomes related to lower respiratory tract infection and for 364 days to assess safety. The primary end point was RSV-associated, medically significant lower respiratory tract infection up to 90 days of life, and the primary analysis of vaccine efficacy against the primary end point was performed in the per-protocol population of infants (prespecified criterion for success, lower bound of the 97.52% confidence interval [CI] of ≥30%). RESULTS: A total of 4636 women underwent randomization, and there were 4579 live births. During the first 90 days of life, the percentage of infants with RSV-associated, medically significant lower respiratory tract infection was 1.5% in the vaccine group and 2.4% in the placebo group (vaccine efficacy, 39.4%; 97.52% CI, -1.0 to 63.7; 95% CI, 5.3 to 61.2). The corresponding percentages for RSV-associated lower respiratory tract infection with severe hypoxemia were 0.5% and 1.0% (vaccine efficacy, 48.3%; 95% CI, -8.2 to 75.3), and the percentages for hospitalization for RSV-associated lower respiratory tract infection were 2.1% and 3.7% (vaccine efficacy, 44.4%; 95% CI, 19.6 to 61.5). Local injection-site reactions among the women were more common with vaccine than with placebo (40.7% vs. 9.9%), but the percentages of participants who had other adverse events were similar in the two groups. CONCLUSIONS: RSV F protein nanoparticle vaccination in pregnant women did not meet the prespecified success criterion for efficacy against RSV-associated, medically significant lower respiratory tract infection in infants up to 90 days of life. The suggestion of a possible benefit with respect to other end-point events involving RSV-associated respiratory disease in infants warrants further study. (Funded by Novavax and the Bill and Melinda Gates Foundation; ClinicalTrials.gov NCT02624947.).

Improving vaccination rates in older adults and at-risk groups: focus on pertussis.

Despite the implementation of effective paediatric vaccination programmes, pertussis remains a global health problem. Disease epidemiology has changed over time, shifting towards the adolescent and adult populations. In adults, the true burden of pertussis is greatly underestimated and pertussis vaccine coverage rates are suboptimal, including individuals with chronic conditions. Here, we report the outcomes of a virtual international scientific workshop to assess the evidence on the burden of pertussis in older adults and identify potential solutions to improve uptake of pertussis vaccines. In adults, pertussis is underdiagnosed in part due to atypical or milder clinical presentation and the lack of testing and case confirmation. However, contemporary epidemiological data denoted an increase in the burden of pertussis among adolescents and adults. This might be related to a variety of reasons including the waning of immunity over time, the lack of booster vaccination, and the improved diagnostic methods that led to increased recognition of the disease in adults. Pertussis sequelae can be severe in older adults, particularly those with existing chronic medical conditions, and the vulnerability of these groups is further enhanced by low pertussis vaccine coverage. Possible measures to increase vaccine uptake include strengthening and harmonisation of immunisation guidelines, healthcare professionals taking a more active role in recommending pertussis vaccination, involvement of vaccination centres and pharmacies in the vaccination process, and improving knowledge of pertussis burden and vaccine efficacy among the general population.

The Safety of Influenza and Pertussis Vaccination in Pregnancy in a Cohort of Australian Mother-Infant Pairs, 2012-2015: The FluMum Study.

Background: Inactivated influenza vaccine (IIV) and pertussis vaccination are recommended in pregnancy. Limited safety data exist for women who received IIV vaccine during the first trimester of pregnancy or received both vaccines in pregnancy. We assessed adverse birth outcomes between vaccinated and unvaccinated pregnancies. Methods: Among prospectively enrolled Australian "FluMum" participants (2012-2015), primary exposure was receipt and timing of IIV during pregnancy. Primary outcomes included preterm birth, low birthweight at term (LBWT), and small for gestational age (SGA). We compared birth outcomes for IIV in pregnancy with women unvaccinated in pregnancy using Cox proportional hazard ratios (HRs) with 95% confidence intervals (CIs). Adjusted HRs (aHRs) controlled for potential confounding variables. Sensitivity analyses were conducted in a subgroup of women who received pertussis vaccination during pregnancy to assess whether associations between IIV and adverse outcomes were maintained after adjusting for pertussis vaccination. Results: Among 8827 participants in our study, women who received IIV in pregnancy did not have an elevated risk of an adverse birth outcome compared with unvaccinated pregnant women: preterm births (HR, 1.10 [95% CI, .92-1.31]; P = .28); LBWT (HR, 1.05 [95% CI, .76-1.44]; P = .77); or SGA (HR, 0.99 [95% CI, .86-1.15]; P = .94). Adjustment for pertussis vaccination during pregnancy yielded similar results: preterm births (aHR, 1.05 [95% CI, .82-1.34]; P = .69); LBWT (aHR, 0.81 [95% CI, .50-1.29]; P = .37); SGA (aHR, 0.92 [95% CI, .74-1.14]; P = .43). There was no evidence of elevated risk by trimester of IIV. Conclusions: No significant associations were found between maternal IIV or pertussis vaccination in pregnancy and adverse birth outcomes, regardless of the trimester of pregnancy a vaccination was given compared to unvaccinated pregnancies.

Influenza and pertussis vaccination of women during pregnancy in Victoria, 2015-2017.

OBJECTIVES: To assess variations by time of year and hospital in the uptake of influenza and pertussis vaccinations by pregnant women in Victoria; to identify factors associated with vaccination uptake. DESIGN, SETTING: Retrospective analysis of data in the Victorian Perinatal Data Collection (VPDC), a population surveillance system for obstetric conditions, procedures, and pregnancy and birth outcomes. PARTICIPANTS: Women whose pregnancies ended in a live or stillbirth during July 2015 - June 2017. MAIN OUTCOME MEASURES: Influenza and pertussis vaccinations during pregnancy. RESULTS: 153 980 pregnancies in 67 hospitals ended during July 2015 - June 2017; 59 968 pregnant women (39.0%) were vaccinated against influenza and 98 583 (64.0%) against pertussis. Coverage varied by pregnancy end date, rising for influenza during winter and spring, but for pertussis rising continuously across the two years from 37.5% to 82.2%. Differences between hospitals in coverage were marked. Factors associated with vaccination included greater maternal age, primigravidity, early antenatal care, and GP-led care. The odds of vaccination were statistically significantly lower for women born overseas and those who smoked during pregnancy; the odds of vaccination were also lower for Aboriginal and Torres Strait Islander women. CONCLUSIONS: Pertussis vaccination of pregnant women in Victoria has increased, but influenza vaccination rates remain moderate and variable. Structural changes at the system level may improve maternal vaccination rates. Embedding the delivery of maternal vaccination programs in antenatal care pathways should be a priority.

Socioeconomic and health factors associated with kindergarten retention in Australian children.

AIM: We aimed to identify key socioeconomic and health factors that are associated with a child's likelihood of being retained in kindergarten prior to commencing first year of school in Australian children. METHODS: We used data linked from the School Entrant Health Questionnaire administered to children commencing school in 2012 (N = 42 002). Kindergarten retention here is defined by children accessing a second year of funded kindergarten prior to commencing school. We used logistic regression analysis to estimate the strength of associations between a range of socioeconomic and health factors to the likelihood of kindergarten retention. RESULTS: Of the 25 289 children included in our analysis, 903 (3.6%) had a second year of funded kindergarten prior to commencing school. In comparison, 1680 children out of 42 002 in the Kinder-School Entrant Health Questionnaire dataset had a second year of funded kindergarten (4.0%). From our final regression model, the highest association was found in children whose parents reported a history of speech and language difficulties (odds ratio 2.25, 95% confidence interval (1.91-2.66)) (adjusting for a range of demographic, health and developmental factors). Similarly, children from an indigenous background were twice as likely to be retained in kindergarten compared with those with a non-indigenous background (odds ratio 2.06 (1.17-3.64)). CONCLUSION: This analysis adds to the evidence base that children who are more socially disadvantaged as well as children with health difficulties, particularly speech and language difficulties, are more likely to be retained in kindergarten.

Prevalence and Incidence of Respiratory Syncytial Virus and Other Respiratory Viral Infections in Children Aged 6 Months to 10 Years With Influenza-like Illness Enrolled in a Randomized Trial.

BACKGROUND: The high burden of respiratory syncytial virus (RSV)-associated morbidity and mortality makes vaccine development a priority. METHODS: As part of an efficacy trial of pandemic influenza vaccines (NCT01051661), RSV epidemiology in healthy children aged 6 months to <10 years at first vaccination with influenza-like illness (ILI) was evaluated in Australia, Brazil, Colombia, Costa Rica, Mexico, the Philippines, Singapore, and Thailand between February 2010 and August 2011. Active surveillance for ILI was conducted for approximately 1 year, with nasal and throat swabs analyzed by polymerase chain reaction. The prevalence and incidence of RSV among ILI episodes were calculated. RESULTS: A total of 6266 children were included, of whom 2421 experienced 3717 ILI episodes with a respiratory sample available. RSV was detected for 359 ILI episodes, a prevalence of 9.7% (95% confidence interval: 8.7-10.7). The highest prevalence was in children aged 12-23 or 24-35 months in all countries except the Philippines, where it was in children aged 6-11 months. The incidence of RSV-associated ILI was 7.0 (6.3-7.7) per 100 person-years (PY). Eighty-eight ILI episodes resulted in hospitalization, of which 8 were associated with RSV (prevalence 9.1% [4.0-17.1]; incidence 0.2 [0.1-0.3] per 100 PY). The incidence of RSV-associated ILI resulting in medical attendance was 6.0 (5.4-6.7) per 100 PY. RSV B subtypes were observed more frequently than A subtypes. CONCLUSIONS: Active surveillance demonstrated the considerable burden of RSV-associated illness that would not be identified through hospital-based surveillance, with a substantial part of the burden occurring in older infants and children.

The Influence of Social Disadvantage on Children's Emotional and Behavioral Difficulties at Age 4-7 Years.

OBJECTIVE: To examine associations between indicators of social disadvantage and emotional and behavioral difficulties in children aged 4-7 years. STUDY DESIGN: This cross-sectional study was based on data collected in a questionnaire completed by parents of children enrolled in their first year of school in Victoria, Australia, in 2010. Just over 57000 children participated (86% of children enrolled), of whom complete data were available for 38955 (68% of the dataset); these children formed the analysis sample. The outcome measure was emotional and behavioral difficulties, assessed by the Strengths and Difficulties Questionnaire Total Difficulties score. Logistic regression analyses were undertaken. RESULTS: Having a concession card (a government-issued card enabling access to subsidized goods and services, particularly in relation to medical care, primarily for economically vulnerable households) was the strongest predictor of emotional and behavioral difficulties (OR, 2.71; 95% CI, 2.39-3.07), followed by living with 1 parent and the parent's partner or not living with either parent (OR, 1.93; 95% CI, 1.58-2.37) and having a mother who did not complete high school (OR, 1.27; 95% CI, 1.11-1.45). CONCLUSION: These findings may assist schools and early childhood practitioners in identifying young children who are at increased risk of emotional and behavioral difficulties, to provide these children, together with their parents and families, with support from appropriate preventive interventions.

Normative data for the Strengths and Difficulties Questionnaire for young children in Australia.

AIM: The aim of this study was to report normative data for the parent-reported Strengths and Difficulties Questionnaire (SDQ) from a large population cohort of young children aged 4-6 years from Victoria, Australia, to establish age- and sex-specific cut-off values for future use, and to determine the scale reliability of the SDQ for children aged 4-6 years. METHODS: Parents of children (n = 53 372) entering their first year of school in Victoria in 2010 completed a survey via a 15-page School Entrant Health Questionnaire reporting on the physical and emotional well-being of their child (including the SDQ), use of child health and other support services, and a range of socio-demographic variables. Reliability was assessed and norms generated. Appropriate cut-off values for each SDQ scale and total difficulties scale were generated for each age group separately for each sex. RESULTS: The five scales of the SDQ and total difficulties scale generally had acceptable internal reliability. Mean SDQ scale scores differed for both sex and age, although only a narrow age range is examined in this study. Cut-off values were marginally higher for girls (lower for prosocial) and generally increased with age. CONCLUSIONS: This study has utilised a large Australian population sample of children to generate age- and sex-specific cut-off values that define SDQ scores as 'normal', 'borderline' or 'abnormal' for Australian children aged 4-6 years.

Heterologous prime-boost vaccination using an AS03B-adjuvanted influenza A(H5N1) vaccine in infants and children<3 years of age.

BACKGROUND: Protecting young children from pandemic influenza should also reduce transmission to susceptible adults, including pregnant women. METHODS: An open study assessed immunogenicity and reactogenicity of a heterologous booster dose of A/turkey/Turkey/1/2005(H5N1)-AS03B (AS03B is an Adjuvant System containing α-tocopherol and squalene in an oil-in-water emulsion [5.93 mg tocopherol]) in infants and children aged 6 to <36 months that was given 6 months following 2-dose primary vaccination with A/Indonesia/05/2005(H5N1)-AS03B. Vaccines contained 1.9 µg of hemagglutinin antigen and AS03B. Hemagglutinin inhibition (HI) responses, microneutralization titers, and antineuraminidase antibody levels were assessed for 6 months following the booster vaccination. RESULTS: For each age stratum (defined on the basis of the subject's age at first vaccination as 6 to <12 months, 12 to <24 months, and 24 to <36 months) and overall (n=113), European influenza vaccine licensure criteria were fulfilled for responses to A/turkey/Turkey/1/2005(H5N1) 10 days following the booster vaccination. Local pain and fever increased with consecutive doses. Anamnestic immune responses were demonstrated for HI, neutralizing, and antineuraminidase antibodies against vaccine-homologous/heterologous strains. Antibody responses to vaccine-homologous/heterologous strains persisted in all children 6 months following the booster vaccination. CONCLUSIONS: Prevaccination of young children with a clade 2 strain influenza A(H5N1) AS03-adjuvanted vaccine followed by heterologous booster vaccination boosted immune responses to the homologous strain and a related clade, with persistence for at least 6 months. The results support a prime-boost vaccination approach in young children for pandemic influenza preparedness. CLINICAL TRIALS REGISTRATION: NCT01323946.

Relative efficacy of AS03-adjuvanted pandemic influenza A(H1N1) vaccine in children: results of a controlled, randomized efficacy trial.

BACKGROUND: The vaccine efficacy (VE) of 1 or 2 doses of AS03-adjuvanted influenza A(H1N1) vaccine relative to that of 2 doses of nonadjuvanted influenza A(H1N1) vaccine in children 6 months to <10 years of age in a multinational study conducted during 2010-2011. METHODS: A total of 6145 children were randomly assigned at a ratio of 1:1:1 to receive 2 injections 21 days apart of A/California/7/2009(H1N1)-AS03 vaccine at dose 1 and saline placebo at dose 2, 2 doses 21 days apart of A/California/7/2009(H1N1)-AS03 vaccine (the Ad2 group), or 2 doses 21 days apart of nonadjuvanted A/California/7/2009(H1N1) vaccine (the NAd2 group). Active surveillance for influenza-like illnesses continued from days 14 to 385. Nose and throat samples obtained during influenza-like illnesses were tested for A/California/7/2009(H1N1), using reverse-transcriptase polymerase chain reaction. Immunogenicity, reactogenicity, and safety were assessed. RESULTS: There were 23 cases of confirmed 2009 pandemic influenza A(H1N1) (A[H1N1]pdm09) infection for the primary relative VE analysis. The VE in the Ad2 group relative to that in the NAd2 group was 76.8% (95% confidence interval, 18.5%-93.4%). The benefit of the AS03 adjuvant was demonstrated in terms of the greater immunogenicity observed in the Ad2 group, compared with the NAd2 group. CONCLUSION: The 4-8-fold antigen-sparing adjuvanted pandemic influenza vaccine demonstrated superior and clinically important prevention of A(H1N1)pdm09 infection, compared with nonadjuvanted vaccine, with no observed increase in medically attended or serious adverse events. These data support the use of adjuvanted influenza vaccines during influenza pandemics. Clinical Trials Registration. NCT01051661.

Detection of a divergent Parainfluenza 4 virus in an adult patient with influenza like illness using next-generation sequencing.

BACKGROUND: Human Parainfluenza viruses are a common cause of both upper and lower respiratory tract infections, particularly in children. Of the four Parainfluenza virus serotypes, Parainfluenza 4 is least well characterised from both the clinical, epidemiological and genetic perspectives. METHODS: Flocked nose or throat swabs from a previous study investigating viral prevalence in community-based adults suffering from influenza like illness were used as the basis for this study. Samples in which no virus was detected using a 16 viral respiratory pathogen real-time PCR panel were barcoded and pyrosequenced using the Roche 454 GS FLX Titanium chemistry. The sequences were analysed using the VirusHunter bioinformatic pipeline. Sanger sequencing was used to complete the detected Parainfluenza 4 coding region. RESULTS: A variant Parainfluenza 4 subtype b strain (QLD-01) was discovered in an otherwise healthy adult who presented with influenza like illness. Strain QLD-01 shared genomic similarities with both a and b subtypes. The extent of divergence of this genome from the 5 available whole Parainfluenza 4 genomes impacted the predicted binding efficiencies of the majority of published Parainfluenza 4 PCR assays. CONCLUSIONS: These findings further support a possible role for Parainfluenza 4 in the aetiology of adult respiratory disease within the community setting, and highlight the caution needed to be used in designing PCR assays from limited sequence information or in using proprietary commercial PCR assays.

A positive approach to parents with concerns about vaccination for the family physician.

BACKGROUND: Vaccine hesitancy is becoming increasingly recognised as an issue in Australia and globally, as concerns about vaccines and their safety predominate over concerns about the risk of vaccine-preventable diseases. OBJECTIVE: This review provides an approach for primary care physicians to enable effective communication with parents who have differ-ent levels of concerns about vaccinations and awareness of currently available resources that may be used to support discussions. DISCUSSION: Clear and flexible communication strategies for healthcare providers to undertake effective discussions with vaccine-hesitant parents or clear referral pathways are the key to addressing concerns about vaccination in both primary and secondary care.

The Platform Technology Approach to mRNA Product Development and Regulation.

mRNA-lipid nanoparticle (LNP) medicinal products can be considered a platform technology because the development process is similar for different diseases and conditions, with similar noncoding mRNA sequences and lipid nanoparticles and essentially unchanged manufacturing and analytical methods often utilised for different products. It is critical not to lose the momentum built using the platform approach during the development, regulatory approval and rollout of vaccines for SARS-CoV-2 and its variants. This review proposes a set of modifications to existing regulatory requirements for mRNA products, based on a platform perspective for quality, manufacturing, preclinical, and clinical data. For the first time, we address development and potential regulatory requirements when the mRNA sequences and LNP composition vary in different products as well. In addition, we propose considerations for self-amplifying mRNA, individualised oncology mRNA products, and mRNA therapeutics. Providing a predictable development pathway for academic and commercial groups so that they can know in detail what product characterisation and data are required to develop a dossier for regulatory submission has many potential benefits. These include: reduced development and regulatory costs; faster consumer/patient access and more agile development of products in the face of pandemics; and for rare diseases where alternatives may not exist or to increase survival and the quality of life in cancer patients. Therefore, achieving consensus around platform approaches is both urgent and important. This approach with mRNA can be a template for similar platform frameworks for other therapeutics and vaccines to enable more efficient development and regulatory review.

4CMenB journey to the 10-year anniversary and beyond.

The 4-component meningococcal serogroup B (MenB) vaccine, 4CMenB, the first broadly protective, protein-based MenB vaccine to be licensed, is now registered in more than 50 countries worldwide. Real-world evidence (RWE) from the last decade confirms its effectiveness and impact, with infant immunization programs showing vaccine effectiveness of 71-95% against invasive MenB disease and cross-protection against non-B serogroups, including a 69% decrease in serogroup W cases in 4CMenB-eligible cohorts in England. RWE from different countries also demonstrates the potential for additional moderate protection against gonorrhea in adolescents. The real-world safety profile of 4CMenB is consistent with prelicensure reports. Use of the endogenous complement human serum bactericidal antibody (enc-hSBA) assay against 110 MenB strains may enable assessment of the immunological effectiveness of multicomponent MenB vaccines in clinical trial settings. Equitable access to 4CMenB vaccination is required to better protect all age groups, including older adults, and vulnerable groups through comprehensive immunization policies.

Invasive meningococcal disease, caused by the bacterium Neisseria meningitidis(meningococcus), is rare but often devastating and can be deadly. Effective vaccines are available, including vaccines against meningococcal serogroup B disease. In 2013, the 4-component meningococcal serogroup B vaccine, 4CMenB, became the first broadly protective, protein-based vaccine against serogroup B to be licensed, with the second (bivalent vaccine, MenB-FHbp) licensed the following year. 4CMenB is now registered in more than 50 countries, in the majority, for infants and all age groups. In the US, it is approved for individuals aged 10­25 years. Evidence from immunization programs in the last decade, comparing vaccinated and unvaccinated individuals and the same population before and after vaccination, confirms the effectiveness and positive impact of 4CMenB against serogroup B disease. This also demonstrates that 4CMenB can provide protection against invasive diseases caused by other meningococcal serogroups. Furthermore, N. meningitidis is closely related to the bacterium that causes gonorrhea, N. gonorrhoeae, and emerging real-world evidence suggests that 4CMenB provides additional moderate protection against gonococcal disease. The safety of 4CMenB when given to large numbers of infants, children, adolescents, and adults is consistent with the 4CMenB safety profile reported before licensure.For the future, it would be beneficial to address differences among national guidelines for the recommended administration of 4CMenB, particularly where there is supportive epidemiological evidence but no equitable access to vaccination. New assays for assessing the potential effectiveness of meningococcal serogroup B vaccines in clinical trials are also required because serogroup B strains circulating in the population are extremely diverse across different countries.

Public health management of pertussis in adults: Practical challenges and future strategies.

A panel of 24 international experts met in July 2022 to discuss challenges associated with pertussis detection, monitoring, and vaccination in adults; conclusions from this meeting are presented. There has been a shift in the epidemiology of pertussis toward older children and adults. This shift has been attributed to the waning of infection- or vaccine-induced immunity, newer detection techniques causing detection bias, and possibly the replacement of whole-cell pertussis with acellular vaccines in high-income countries, which may lead to immunity waning more quickly. The burden of adult pertussis is still likely under-ascertained due to widespread under-recognition by healthcare professionals (HCPs), under-diagnosis, and under-reporting in this age group. Non-standardized testing guidance and varied case definitions have contributed to under-reporting. Key barriers to HCP engagement with the tetanus, diphtheria, and pertussis (Tdap) vaccine include low awareness, lack of time/funding, and lack of motivation due to low prioritization of Tdap.

Understanding the impact of adult pertussis and current approaches to vaccination: A narrative review and expert panel recommendations.

Pertussis has several notable consequences, causing economic burden, increased strain on healthcare facilities, and reductions in quality of life. Recent years have seen a trend toward an increase in pertussis cases affecting older children and adults. To boost immunity, and protect vulnerable populations, an enduring approach to vaccination has been proposed, but gaps remain in the evidence surrounding adult vaccination that are needed to inform such a policy. Gaps include: the true incidence of pertussis and its complications in adults; regional variations in disease recognition and reporting; and incidence of severe disease, hospitalizations, and deaths in older adults. Better data on the efficacy/effectiveness of pertussis vaccination in adults, duration of protection, and factors leading to poor vaccine uptake are needed. Addressing the critical evidence gaps will help highlight important areas of unmet need and justify the importance of adult pertussis vaccination to healthcare professionals, policymakers, and payers.

Excess mortality among people with communicable diseases over a 30-year period, Victoria, Australia: a whole of population cohort study.

Background: Understanding mortality burden associated with communicable diseases is key to informing resource allocation, disease prevention and control efforts, and evaluating public health interventions. We quantified excess mortality among people notified with communicable diseases in Victoria, Australia. Methods: Cases of communicable disease notified in Victoria between 1 January 1991 and 31 December 2021 were linked to the death registry. Informational gain obtained through linkage and 30-day case fatality rates were calculated for each disease. Standardised mortality ratios (SMR) and 95% confidence intervals were calculated up to a year following illness onset. Findings: There were 1,032,619 cases and 5985 (0.58%) died ≤30 days of illness onset. Following linkage, the 30-day case fatality rate increased more than 2-fold. Diseases with high 7-day SMR signifying excess mortality included invasive pneumococcal disease (167.7, 95% CI 153.4-182.7); listeriosis (166.2, 95% CI 121.2-218.3); invasive meningococcal disease (145.9, 95% CI 116.7-178.3); legionellosis (43.3, 95% CI 28.0-62.0); and COVID-19 (21.9, 95% CI 19.7-24.3). Most diseases exhibited a strong negative gradient, with high SMRs in the first 7-days of illness onset that reduced over time. Interpretation: We demonstrated that the rate of death in Victoria's notifiable disease surveillance dataset is underestimated. Further, compared to a general population, there is evidence of elevated all-cause mortality among people notified with communicable diseases often up to one year following illness onset. Not all elevated risk is likely directly attributable to the communicable diseases of interest, rather, it may reflect underlying comorbidities or behaviours in these individuals. Regardless of attribution, infection with communicable diseases may represent a marker of mortality. Key to preventing deaths may be through timely and appropriate transition to primary and preventive healthcare following diagnosis. Funding: No funding was provided for this study.