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.

Field evaluation of rapid diagnostic tests to determine dengue serostatus in Timor-Leste.

The live attenuated tetravalent CYD-TDV vaccine (Dengvaxia) is effective but has scarcely been used due to safety concerns among seronegative recipients. Rapid diagnostic tests (RDTs) which can accurately determine individual dengue serostatus are needed for use in pre-vaccination screening. This study aimed to determine the performance of existing RDTs (which have been designed to detect levels of immunoglobulin G, IgG, associated with acute post-primary dengue) when repurposed for detection of previous dengue infection (where concentrations of IgG are typically lower). A convenience sample of four-hundred-and-six participants including 217 children were recruited during a community serosurvey. Whole blood was collected by phlebotomy and tested using Bioline Dengue IgG/IgM (Abbott) and Standard Q Dengue IgM/IgG (SD Biosensor) RDTs in the field. Serum samples from the same individuals were also tested at National Health Laboratory. The Panbio indirect IgG ELISA was used as a reference test. Reference testing determined that 370 (91.1%) participants were dengue IgG seropositive. Both assays were highly specific (100.0%) but had low sensitivity (Bioline = 21.1% and Standard Q = 4.6%) when used in the field. Sensitivity was improved when RDTs were used under laboratory conditions, and when assays were allowed to run beyond manufacturer recommendations and read at a delayed time-point, but specificity was reduced. Efforts to develop RDTs with high sensitivity and specificity for prior dengue infection which can be operationalised for pre-vaccination screening are ongoing. Performance of forthcoming candidate assays should be tested under field conditions with blood samples, as well as in the laboratory.

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.