Seroprevalence and prevention of hepatitis B, measles and rubella among healthcare workers in Dili, Timor-Leste.

Introduction: The World Health Organisation recommends that healthcare workers (HCWs) are immune to measles and rubella, and those at risk of exposure are offered the hepatitis B vaccine. No formal programme for occupational assessment and provision of vaccinations to HCWs currently exists in Timor-Leste. Methods: A cross-sectional study was undertaken to determine the seroprevalence of hepatitis B, measles and rubella among HCWs in Dili, Timor-Leste. All patient-facing employees at three healthcare institutions during April-June 2021 were invited to participate. Epidemiological data were collected by interview-questionnaire and a serum sample was collected by phlebotomy and analysed at the National Health Laboratory. Participants were contacted to discuss their results. Relevant vaccines were offered to seronegative individuals and those with active hepatitis B infection were referred for further assessment and management in a hepatology clinic as per national guidelines. Results: Three-hundred-and-twenty-four HCWs were included (representing 51.3% of all eligible HCWs working at the three participating institutions). Sixteen (4.9%; 95% CI: 2.8-7.9%) had active hepatitis B infection, 121 (37.3%; 95% CI: 32.1-42.9%) had evidence of previous (cleared) hepatitis B infection, 134 (41.4%; 95% CI: 35.9-46.9%) were hepatitis B seronegative, and 53 (16.4%; 95% CI: 12.5-20.8%) had been vaccinated. Two-hundred-and-sixty-seven (82.4%; 95% CI: 77.8-86.4%) and 306 (94.4%; 95% CI: 91.4-96.7%) individuals exhibited antibodies to measles and rubella, respectively. Interpretation: There are significant immunity gaps and a high prevalence of hepatitis B infection among HCWs in Dili Municipality, Timor-Leste. Routine occupational assessment and targeted vaccination of this group would be beneficial and should include all types of HCWs. This study provided an opportunity to develop a programme for the occupational assessment and vaccination of HCWs and forms the template for a national guideline. Funding: This work was supported by the Department of Foreign Affairs and Trade, Australian Government [Complex Grant Agreement Number 75889].

Vaccine Preventable Disease Seroprevalence in a Nationwide Assessment of Timor-Leste (VASINA-TL): study protocol for a population-representative cross-sectional serosurvey.

INTRODUCTION: Historic disruption in health infrastructure combined with data from a recent vaccine coverage survey suggests there are likely significant immunity gaps to vaccine preventable diseases and high risk of outbreaks in Timor-Leste. Community-based serological surveillance is an important tool to augment understanding of population-level immunity achieved through vaccine coverage and/or derived from prior infection. METHODS AND ANALYSIS: This national population-representative serosurvey will take a three-stage cluster sample and aims to include 5600 individuals above 1 year of age. Serum samples will be collected by phlebotomy and analysed for measles IgG, rubella IgG, SARS-CoV-2 antispike protein IgG, hepatitis B surface antibody and hepatitis B core antigen using commercially available chemiluminescent immunoassays or ELISA. In addition to crude prevalence estimates and to account for differences in Timor-Leste's age structure, stratified age-standardised prevalence estimates will be calculated, using Asia in 2013 as the standard population. Additionally, this survey will derive a national asset of serum and dried blood spot samples which can be used for further investigation of infectious disease seroepidemiology and/or validation of existing and novel serological assays for infectious diseases. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Research Ethics and Technical Committee of the Instituto Nacional da Saúde, Timor-Leste and the Human Research Ethics Committee of the Northern Territory Department of Health and Menzies School of Health Research, Australia. Co-designing this study with Timor-Leste's Ministry-of-Health and other relevant partner organisations will allow immediate translation of findings into public health policy, which may include changes to routine immunisation service delivery and/or plans for supplementary immunisation activities.

The use of residual serum samples to perform serological surveillance of severe acute respiratory syndrome coronavirus 2 in Dili and regional areas of Timor-Leste.

BACKGROUND: Lack of access to diagnostic testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can limit disease surveillance in remote areas. Serological surveillance can indicate the true extent and distribution of infections in such settings. METHODS: This study monitored SARS-CoV-2 seroprevalence in residual serum samples salvaged from laboratories at five healthcare facilities across Timor-Leste from March to October 2021. RESULTS: Seroprevalence increased from 8.3% to 87.0% during the study period. Potential immunity gaps were identified among children aged 0-15 y (who had not been eligible for vaccination) and individuals aged >60 y. CONCLUSIONS: Efforts to vaccinate vulnerable individuals including older people should be maintained. Residual serum samples can be analysed to give local, contemporary information about the extent and distribution of antibodies to infections, especially SARS-CoV-2, in areas where epidemiological information is limited.

Serological surveillance of healthcare workers to evaluate natural infection- and vaccine-derived immunity to SARS-CoV-2 during an outbreak in Dili, Timor-Leste.

Background Serosurveillance can be used to investigate the extent and distribution of immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within a population. Characterisation of humoral immune responses gives insight into whether immunity is infection- or vaccine-derived. Methods A longitudinal study of health care workers (HCWs) in Dili, Timor-Leste, was conducted during vaccine rollout (ChAdOx1) and a concurrent SARS-CoV-2 outbreak. Results A total of 324 HCWs were included at baseline (April-May 2021). Out of those, 32 (9.9%) were seropositive for anti-nucleocapsid protein (anti-N) IgG antibodies, indicating a significant sub-clinical infection among HCWs early in the local outbreak. Follow-up was conducted in 157 (48.5%) participants (July-September 2021), by which time there had been high uptake of vaccination (91.7%), and 86.0% were seropositive for anti-spike protein antibodies. Acquisition of anti-N antibodies was observed in partially vaccinated HCWs (30/76, 39.5%), indicating some post-dose-1 infections. Discussion Serosurveillance of HCWs may provide early warning of SARS-CoV-2 outbreaks and should be considered in non-endemic settings, particularly where there is limited availability/uptake of testing for acute infection. Characterisation of humoral immune responses may be used to assess vaccine impact and coverage. Such studies should be considered in national and international efforts to investigate and mitigate against future emerging pathogens.

Perinatal immunoprophylaxis in babies born to hepatitis B virus-positive mothers in Queensland Australia: A data linkage study.

Vertical transmission from mother-to-child is an important mode of hepatitis B virus (HBV) infection, accounting for up to half of all incident cases globally. We evaluated the uptake of HBV neonatal vaccination and immunoglobulin delivery in Queensland, Australia, between 2001 and 2013. We identified HBV-positive mothers using linked notifiable conditions, hospitalisation, and perinatal administrative data. Perinatal receipt of monovalent HBV vaccine and hepatitis B immunoglobulin were examined. Of 710,859 live births, with 5753 infants (0.81%) born to identified HBV-positive mothers; 91.7% received HBV neonatal vaccine. Immunoglobulin uptake was 20.0% in 2012 and 36.6% in 2013. Uptake was higher when the mother's HBV-positive status was recorded in perinatal records (69.6% if maternal HBV status recorded on perinatal data collection vs 9.5% otherwise). Delivery of neonatal HBV vaccination in Queensland was high. Improved identification and documentation of HBV-positive mothers' status during the antenatal period was associated with increased immunoglobulin administration.

Impact and effectiveness of childhood varicella vaccine program in Queensland, Australia.

BACKGROUND: In November 2005, Australia introduced a publicly funded single dose of varicella vaccine for children aged 18-months. We describe the impact of this program on varicella hospitalisations in Queensland and provide the first assessment of single-dose varicella vaccine effectiveness in Australia since the program commenced. METHODS: Age-standardised varicella hospitalisation rates were calculated for 2000-2014 and pre- and post-public funding period rates compared. Case-control studies were conducted to investigate the association between vaccine receipt and both varicella hospitalisations and uncomplicated varicella emergency department presentations. Cases were matched to controls from a population-based register by date of birth and state of residence. Vaccine effectiveness was calculated as (1-odds ratio)×100%. RESULTS: Compared to the pre-funded period (2000-2003), age-standardised varicella hospitalisation rates declined by more than 70% in 2011-2014 with varicella principal diagnosis rates declining from 5.7 to 1.6 per 100,000 population per year. Varicella vaccine effectiveness at preventing hospitalisation with a principal diagnosis of varicella among children aged 19-months to 6-years was 81.9% (95% confidence interval: 61.8-91.4%), while for emergency department presentations among children aged 19-months to 8-years it was 57.9% (95% confidence interval: 48.5-65.5%). CONCLUSIONS: In Australia, the single-dose varicella vaccination program has substantially reduced varicella morbidity. The single-dose varicella vaccine schedule is moderately-to-highly effective against hospitalisation, but appears less effective against emergency department presentations.

Febrile Seizures in the Era of Rotavirus Vaccine.

A protective association between rotavirus vaccination and childhood seizures in the year after vaccination was recently reported from the United States. In the state of Queensland, Australia, the authors found that rotavirus vaccine was 35.8% and 38.0% effective at preventing emergency department presentation and subsequent hospitalization, respectively, for febrile seizures among children up to two years following vaccination.

Reduced risk of pertussis in whole-cell compared to acellular vaccine recipients is not confounded by age or receipt of booster-doses.

Several observational studies provide evidence that acellular pertussis vaccines (aP) are less protective against pertussis disease than highly effective whole-cell pertussis vaccines (wP), however, concerns have been raised that some of these findings may be confounded by age. By undertaking age-stratified and restricted analyses on a cohort of Australian children primed with either aP-only, wP-only or mixed pertussis vaccine schedules, we demonstrate that compared to aP the association of wP with increased protection from pertussis is not confounded by age, nor by aP booster-dose receipt.

Waning vaccine immunity in teenagers primed with whole cell and acellular pertussis vaccine: recent epidemiology.

The recent epidemics of pertussis (whooping cough) in parts of the USA and Australia have led to the largest numbers of annual cases reported in over half a century. These epidemics demonstrated a new pattern, with particularly high rates of disease among pre-adolescents and early adolescents. These high rates of pertussis coincided with the first cohorts vaccinated with purely acellular pertussis vaccine, which replaced whole-cell pertussis (wP) vaccine in the later 1990s in the USA and Australia. Studies undertaken during these epidemics provide new evidence of more rapid waning of acellular pertussis-containing vaccines and longer-term protection from effective wP-containing vaccines. There is evidence that receiving wP as at least the first dose of pertussis-containing vaccine provides greater and more long-lived protection, irrespective of the nature of subsequent doses. This evidence will be reviewed together with the immunobiology associated with both vaccines, and the implications for pertussis control discussed.

Acellular pertussis vaccine effectiveness for children during the 2009-2010 pertussis epidemic in Queensland.

UNLABELLED: OBJECTIVES To assess the effectiveness of three, four and five doses of acellular pertussis vaccine against pertussis notification for children aged 1 - < 4 years and 5 - < 12 years, and the effectiveness of three doses of acellular pertussis vaccine against pertussis hospitalisation for children aged 1 - < 4 years. DESIGN, SETTING AND PARTICIPANTS: A population-based retrospective study of children aged 1 - < 12 years residing in Queensland, Australia, during 2009 and 2010. Routinely collected notification, hospitalisation, testing and vaccination data were used to describe notification rates and testing patterns and to assess vaccine effectiveness (VE) by the screening method. MAIN OUTCOME MEASURES: VE against pertussis notification for children aged 1 - < 4 years and 5 - < 12 years, by birth year, and VE against pertussis hospitalisation for children aged 1 - < 4 years. RESULTS: 1961 notifications and 29 hospitalisations were included in the VE calculations. VE point estimates against pertussis notification and hospitalisation in children aged 1 - < 4 years were similar in 2009 and 2010, and ranged between 83.5% and 89.4%. VE point estimates against notification among children aged 5 - < 12 years were between 71.2% and 87.7% in 2009, and between 34.7% and 70.3% in 2010. The numbers of pertussis tests performed for children, particularly polymerase chain reaction (PCR) tests, increased between 2009 and 2010. CONCLUSIONS: Acellular pertussis vaccine provided good protection within the first years of priming, but this waned as age increased. Changes in pertussis testing behaviour, because of increases in PCR use and awareness, may have contributed to increased pertussis notification rates and lower estimates of VE against notification owing to identification of milder disease.