A brief description of the epidemiology of dengue in Dili, Timor-Leste, 2018-2022.

Abstract: Dengue virus (DENV) infection causes 390 million infections per year and 40,000 deaths globally. It is endemic in many countries in Asia, Africa, the Americas, the Caribbean, and Oceania. Dengue is endemic in Timor-Leste year-round, but peak transmission occurs during the rainy season. We briefly describe the epidemiology of DENV in the Municipality of Dili between 2018 and 2022. There were 6,234 cases notified, with a mean annual incidence rate of 330 cases per 100,000 population. There were 55 deaths (case fatality rate 0.9%). The peak annual incidence (3,904 cases) occurred in 2022 after an outbreak was declared in January of that year; this outbreak included 760 cases of dengue haemorrhagic fever and 35 deaths. The number of outbreak cases requiring hospital treatment exceeded the usual capacity, but facilities established for coronavirus disease 2019 (COVID-19) isolation and treatment were repurposed to meet this demand. Existing strategies of vector control, minimising breeding sites and promoting early presentation for treatment should continue, as should the utilisation of surveillance systems and treatment facilities established during the COVID-19 pandemic. However, dengue incidence remains high, and other dengue control strategies-including the deployment of Wolbachia-infected mosquitoes-should be considered in Timor-Leste.

The first confirmed outbreak of chikungunya reported in Timor-Leste, 2024.

Abstract: Timor-Leste is a mountainous, half-island nation with a population of 1.3 million, which shares a land border with Indonesia and is 550 km from Darwin, Australia. Since independence in 2002, Timor-Leste has achieved significant development; however, high levels of poverty remain. Chikungunya virus (CHIKV) is endemic in over 100 countries in Africa, Asia, Europe and in the Americas. It is transmitted by the bite of infected Aedes aegypti or Ae. albopictus mosquitoes, which are present in Timor-Leste and which contribute to annual rainy-season dengue virus (DENV) outbreaks. Symptomatic people typically suffer from acute onset of fever, usually accompanied by severe arthritis or arthralgia. Joint pain can be debilitating for several days, and may sometimes last for weeks, months or years. Unlike DENV infection which has significant mortality, most people recover completely. Between 2002 and 2023, there were 26 cases of CHIKV notified in Australia who acquired their infection in Timor-Leste; however, laboratory testing capability for CHIKV in Timor-Leste only became available in 2021 using polymerase chain reaction (PCR). The first locally diagnosed case was notified in November 2023. In January 2024, an outbreak of CHIKV was recognised in Timor-Leste for the first time, with 195 outbreak cases reported during 1-31 January 2024; all were PCR positive. There were no cases hospitalised, and no deaths. The median age of cases was 17 years (range 1-76 years); 51% were males. Cases were reported across the country; most (88/195) were from Dili, although the highest incidence was seen in the neighbouring municipality of Ermera (monthly incidence rate of 58.8 cases per 100,000 population). This first reported outbreak of CHIKV in Timor-Leste highlights the need for improved mosquito-borne illness control and response strategies, including minimising breeding sites and promoting early presentation for treatment and differential diagnosis from DENV, and consideration of the deployment of Wolbachia-infected mosquitoes, particularly as they have shown to reduce the transmission of CHIKV, DENV and Zika virus, all of which pose threats in Timor-Leste.

A pilot study investigating severe community-acquired febrile illness through implementation of an innovative microbiological and nucleic acid amplification testing strategy in Timor-Leste (ISIN-MANAS-TL).

Objectives: Acute febrile illness (AFI) causes significant health-seeking, morbidity, and mortality in Southeast Asia. This pilot study aimed to describe presentation, etiology, treatment, and outcomes of patients with AFI at one hospital in Timor-Leste and assessing the feasibility of conducting larger studies in this setting. Methods: Patients attending Hospital Nacional Guido Valadares with tympanic or axillary temperature ≥37.5°C in whom a blood culture was taken as part of routine clinical care were eligible. Participants were followed up daily for 10 days and again after 30 days. Whole blood was analyzed using a real-time quantitative polymerase chain reaction assay detecting dengue virus serotypes 1-4 and other arthropod-borne infections. Results: A total of 82 participants were recruited. Polymerase chain reaction testing was positive for dengue in 14 of 82 (17.1%) participants and blood culture identified a bacterial pathogen in three of 82 (3.7%) participants. Follow-up was completed by 75 of 82 (91.5%) participants. High rates of hospital admission (58 of 82, 70.7%), broad-spectrum antimicrobial treatment (34 of 82, 41.5%), and mortality (9 of 82, 11.0%) were observed. Conclusions: Patients with AFI experience poor clinical outcomes. Prospective observational and interventional studies assessing interventions, such as enhanced diagnostic testing, clinical decision support tools, or antimicrobial stewardship interventions, are required and would be feasible to conduct in this setting.

Bottom-up rather than top-down mechanisms determine mesocarnivore interactions in Norway.

Interactions among coexisting mesocarnivores can be influenced by different factors such as the presence of large carnivores, land-use, environmental productivity, or human disturbance. Disentangling the relative importance of bottom-up and top-down processes can be challenging, but it is important for biodiversity conservation and wildlife management. The aim of this study was to assess how the interactions among mesocarnivores (red fox Vulpes vulpes, badger Meles meles, and pine marten Martes martes) were affected by large carnivores (Eurasian lynx Lynx lynx and wolf Canis lupus), land cover variables (proportion of agricultural land and primary productivity), and human disturbance, as well as how these top-down and bottom-up mechanisms were influenced by season. We analyzed 3 years (2018-2020) of camera trapping observations from Norway and used structural equation models to assess hypothesized networks of causal relationships. Our results showed that land cover variables were more strongly associated with mesocarnivore detection rates than large carnivores in Norway. This might be caused by a combination of low density of large carnivores in an unproductive ecosystem with strong seasonality. Additionally, detection rates of all mesocarnivores showed positive associations among each other, which were stronger in winter. The prevalence of positive interactions among predators might indicate a tendency to use the same areas and resources combined with weak interference competition. Alternatively, it might indicate some kind of facilitative relationship among species. Human disturbance had contrasting effects for different species, benefiting the larger mesocarnivores (red fox and badger) probably through food subsidization, but negatively affecting apex predators (wolf and lynx) and smaller mesocarnivores (pine marten). In a human-dominated world, this highlights the importance of including anthropogenic influences in the study of species interactions.

"Nothing without connection"-Participant perspectives and experiences of mentorship in capacity building in Timor-Leste.

The literature on mentorship approaches to capacity building in global health is limited. Likewise, there are few qualitative studies that describe mentorship in capacity building in global health from the perspective of the mentors and mentees. This qualitative study examined the perspectives and experiences of participants involved in a program of health capacity building in Timor-Leste that was based on a side-by-side, in-country mentorship approach. Semi-structured interviews were conducted with 23 participants (including Timorese and expatriate mentors, and local Timorese colleagues) from across a range of professional health disciplines, followed by a series of member checking workshops. Findings were reviewed using inductive thematic analysis. Participants were included in review and refinement of themes. Four major themes were identified: the importance of trust and connection within the mentoring relationship; the side-by-side nature of the relationship (akompaña); mentoring in the context of external environmental challenges; and the need for the mentoring relationship to be dynamic and evolving, and aligned to a shared vision and goals. The importance of accompaniment (akompaña) as a key element of the mentoring relationship requires further exploration and study. Many activities in global health capacity building remain focused on provision of training, supervision, and supportive supervision of competent task performance. Viewed through a decolonising lens, there is an imperative for global health actors to align with local priorities and goals, and work alongside individuals supporting them in their vision to become independent leaders of their professions. We propose that placing mentoring relationships at the centre of human resource capacity building programs encourages deep learning, and is more likely to lead to long term, meaningful and sustainable change.

National cross-sectional cluster survey of tuberculosis prevalence in Timor-Leste: a study protocol.

INTRODUCTION: Timor-Leste has one of the world's highest estimated tuberculosis (TB) incidences, yet the data which informs this estimate is limited and the true burden of TB disease is not known. TB prevalence surveys offer the best means of determining robust estimates of disease burden. This study aims to provide an estimate of the prevalence of bacteriologically confirmed pulmonary TB in Timor-Leste and provide additional insights into diagnostic coverage and health-seeking behaviour of persons with symptoms suggestive of TB. METHODS AND ANALYSIS: A national population-based cross-sectional cluster survey will be conducted in which participants aged 15 years and older will be screened for pulmonary TB using an algorithm consisting of symptom screening and digital X-ray of the chest with computer-aided detection software for X-ray interpretation. Xpert Ultra and liquid culture methods will be used to confirm survey TB cases. Additional data will be collected from persons reporting symptoms suggestive of TB to assess health-seeking behaviour and access to TB diagnosis and care. The survey aims to screen a target sample population of 20 068 people, living within 50 clusters, representing every municipality of Timor-Leste. Bacteriologically confirmed pulmonary TB prevalence will be estimated using WHO-recommended methods. ETHICS AND DISSEMINATION: Research ethics approval has been granted by the human research ethics committee of the Northern Territory, Australia, and the Instituto Nacional da Saúde, Timor-Leste. The results will be published in a peer-reviewed scientific journal and disseminated with relevant stakeholders. TRIAL REGISTRATION NUMBER: ACTRN12623000718640.

Prevalence of Antimicrobial Resistance in Escherichia coli and Salmonella Species Isolates from Chickens in Live Bird Markets and Boot Swabs from Layer Farms in Timor-Leste.

The rapid emergence of antimicrobial resistance is a global concern, and high levels of resistance have been detected in chicken populations worldwide. The purpose of this study was to determine the prevalence of antimicrobial resistance in Escherichia coli and Salmonella spp. isolated from healthy chickens in Timor-Leste. Through a cross-sectional study, cloacal swabs and boot swabs were collected from 25 live bird markets and two layer farms respectively. E. coli and Salmonella spp. from these samples were tested for susceptibility to six antimicrobials using a disk diffusion test, and a subset was tested for susceptibility to 27 antimicrobials using broth-based microdilution. E. coli and Salmonella spp. isolates showed the highest resistance towards either tetracycline or ampicillin on the disk diffusion test. E. coli from layer farms (odds ratio:5.2; 95%CI 2.0-13.1) and broilers (odds ratio:18.1; 95%CI 5.3-61.2) were more likely to be multi-drug resistant than those from local chickens. Based on the broth-based microdilution test, resistance to antimicrobials in the Timor-Leste Antimicrobial Guidelines for humans were low, except for resistance to ciprofloxacin in Salmonella spp. (47.1%). Colistin resistance in E. coli was 6.6%. Although this study shows that antimicrobial resistance in chickens was generally low in Timor-Leste, there should be ongoing monitoring in commercial chickens as industry growth might be accompanied with increased antimicrobial use.

Characterization of CSF inflammatory markers after hemorrhagic stroke and their relationship to disease severity.

Background: The inflammatory response within the central nervous system is a key driver of secondary brain injury after hemorrhagic stroke, both in patients with intracerebral hemorrhage (ICH) and aneurysmal subarachnoid hemorrhage (aSAH). In this study, we aimed to characterize inflammatory molecules in the blood and cerebrospinal fluid (CSF) of patients within 72 hours of hemorrhage to understand how such molecules vary across disease types and disease severity. Methods: Biological samples were collected from patients admitted to a single-center Neurosciences Intensive Care Unit with a diagnosis of ICH or aSAH between 2014 and 2022. Control CSF samples were collected from patients undergoing CSF diversion for normal pressure hydrocephalus. A panel of immune molecules in the plasma and CSF samples was analyzed using Cytometric Bead Array assays. Clinical variables, including demographics, disease severity, and intensive care unit length of stay were collected. Results: Plasma and/or CSF samples were collected from 260 patients (188 ICH patients, 54 aSAH patients, 18 controls). C-C motif chemokine ligand-2 (CCL2), interleukin-6 (IL-6), granulocyte-colony stimulating factor (G-CSF), interleukin-8 (IL-8), and vascular endothelial growth factor (VEGF), were detectable in the CSF within the first 3 days after hemorrhage, and all were elevated compared to plasma. Compared with controls, CCL2, IL-6, IL-8, G-CSF, and VEGF were elevated in the CSF of both ICH and aSAH patients (p<0.01 for all comparisons). VEGF was increased in ICH patients compared to aSAH patients (p<0.01). CCL2, G-CSF, and VEGF in the CSF were associated with more severe disease in aSAH patients only. Conclusions: Within 3 days of hemorrhagic stroke, proinflammatory molecules can be detected in the CSF at higher concentrations than in the plasma. Early concentrations of some pro-inflammatory molecules may be associated with markers of disease severity.

ACORN (A Clinically-Oriented Antimicrobial Resistance Surveillance Network) II: protocol for case based antimicrobial resistance surveillance.

Background: Antimicrobial resistance surveillance is essential for empiric antibiotic prescribing, infection prevention and control policies and to drive novel antibiotic discovery. However, most existing surveillance systems are isolate-based without supporting patient-based clinical data, and not widely implemented especially in low- and middle-income countries (LMICs). Methods: A Clinically-Oriented Antimicrobial Resistance Surveillance Network (ACORN) II is a large-scale multicentre protocol which builds on the WHO Global Antimicrobial Resistance and Use Surveillance System to estimate syndromic and pathogen outcomes along with associated health economic costs. ACORN-healthcare associated infection (ACORN-HAI) is an extension study which focuses on healthcare-associated bloodstream infections and ventilator-associated pneumonia. Our main aim is to implement an efficient clinically-oriented antimicrobial resistance surveillance system, which can be incorporated as part of routine workflow in hospitals in LMICs. These surveillance systems include hospitalised patients of any age with clinically compatible acute community-acquired or healthcare-associated bacterial infection syndromes, and who were prescribed parenteral antibiotics. Diagnostic stewardship activities will be implemented to optimise microbiology culture specimen collection practices. Basic patient characteristics, clinician diagnosis, empiric treatment, infection severity and risk factors for HAI are recorded on enrolment and during 28-day follow-up. An R Shiny application can be used offline and online for merging clinical and microbiology data, and generating collated reports to inform local antibiotic stewardship and infection control policies. Discussion: ACORN II is a comprehensive antimicrobial resistance surveillance activity which advocates pragmatic implementation and prioritises improving local diagnostic and antibiotic prescribing practices through patient-centred data collection. These data can be rapidly communicated to local physicians and infection prevention and control teams. Relative ease of data collection promotes sustainability and maximises participation and scalability. With ACORN-HAI as an example, ACORN II has the capacity to accommodate extensions to investigate further specific questions of interest.

Strengthening Health Research and Ethics Systems in Timor-Leste.

Introduction: Meaningful health research should lead to evidence-based decision-making that can be translated into policy and practice. Every country needs to have a well-functioning and resourced ethics review and clearance system to ensure health and medical research is conducted in line with ethical standards, preventing harm to research participants, and contributing to better health outcomes and national priorities. The purpose of this study is to describe the origins of the system for managing health research and ethics in Timor-Leste and how it has evolved over time; to identify the strengths and limitations of the current system; and to recommend areas for improvement. Materials and Methods: A narrative review of the literature (published papers, gray literature, and unpublished data) was conducted alongside key informant interviews with 15 Ministry of Health (MOH) policymakers and National Institute of Health staff between October 2020 and March 2021. Results: The system for managing health research and ethics in Timor-Leste has remained largely the same since it was first established in 2009, with some adaptations to cope with a progressively increasing workload. Main findings include: the Department of Research and Studies (DRS) oversees complex ethics approval process in addition to other responsibilities; the DRS lacks the legal authority, policies, and procedures to help implement its full range of functions and responsibilities; national research priorities should be identified; MOH experiences difficulties in securing funding to support health research; training in health research, ethics and governance is an important priority for DRS. Conclusion: It is timely and important to invest in strengthening key components of health research and ethics systems in Timor-Leste. Despite limited resources, improvements can be achieved in key areas with focused assistance and collaboration with local, national, and international partners.

The response to COVID-19 in Timor-Leste: lessons learnt.

The response to the COVID-19 pandemic in Timor-Leste offers lessons that may be useful for incorporating into future responses to infectious disease outbreaks in similar resource-limited settings. In this paper, we identify nine key areas for learning from Timor-Leste's experience of the COVID-19 pandemic: (1) the importance of prior preparation for health emergencies, (2) the establishment of effective leadership and governance structures, (3) the protective impact of early border restrictions, (4) the rapid expansion of diagnostic laboratory capacity, (5) the impact of effective health communications in supporting the vaccine roll-out, (6) the opportunity to build capacity for clinical care, (7) the use of public health interventions that were found to have limited public health impact, (8) the broader effects of the pandemic and the public health response and (9) translation of lessons from COVID-19 to other public health priorities.

Melioidosis in Timor-Leste: First Case Description and Phylogenetic Analysis.

Burkholderia pseudomallei, the causative agent of melioidosis, has not yet been reported in Timor-Leste, a sovereign state northwest of Australia. In the context of improved access to diagnostic resources and expanding clinical networks in the Australasian region, we report the first 3 cases of culture-confirmed melioidosis in Timor-Leste. These cases describe a broad range of typical presentations, including sepsis, pneumonia, multifocal abscesses, and cutaneous infection. Phylogenetic analysis revealed that the Timor-Leste isolates belong to the Australasian clade of B. pseudomallei, rather than the Asian clade, consistent with the phylogeographic separation across the Wallace Line. This study underscores an urgent need to increase awareness of this pathogen in Timor-Leste and establish diagnostic laboratories with improved culture capacity in regional hospitals. Clinical suspicion should prompt appropriate sampling and communication with laboratory staff to target diagnostic testing. Local antimicrobial guidelines have recently been revised to include recommendations for empiric treatment of severe sepsis.

Real-World Use of Electronic Patient-Reported Outcome (ePRO) Tools Integrated in the Electronic Medical Record During Radiation Therapy for Head and Neck Cancer: Feasibility Study.

Purpose Use of electronic patient-reported outcome (ePRO) tools in routine oncology practice can be challenging despite evidence showing they can improve survival, improve patient and practitioner satisfaction, and reduce medical resource utilization. Head and neck cancer (HNC) patients receiving radiation therapy (RT) may be a group that would particularly benefit from interventions focused on early symptom management. Methods Patients undergoing definitive RT for HNC were enrolled in a feasibility study and received ePRO surveys integrated within the electronic medical record (EMR) on a weekly basis during RT. After completion of each ePRO survey, a radiation oncology registered nurse documented the findings and subsequent interventions within the EMR. Results Thirty-four patients with HNC who received curative RT at a single center were enrolled. The total number of surveys completed was 194 with a median of 7 surveys per patient (range 1-8). There was a total of 887 individual abnormal findings reported on the ePROs, and the authors found that all 887 had a corresponding documented intervention. Post-treatment practitioner questionnaires highlighted that ePROs were felt to be helpful for the care team in providing care to HNC patients. Conclusion For patients with HNC receiving RT, ePROs can be effectively utilized to address patient symptoms within an integrated health care system. Creating an infrastructure for the use of ePROs integrated within the EMR in routine care requires an approach that accounts for local workflows and buy-in from patients and the entire care team.

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].

The impact of ivermectin, diethylcarbamazine citrate, and albendazole mass drug administration on the prevalence of scabies and soil-transmitted helminths in school-aged children in three municipalities in Timor-Leste: a before-after assessment.

BACKGROUND: Integrated programmes that use combination mass drug administration (MDA) might improve control of multiple neglected tropical diseases simultaneously. We investigated the impact of Timor-Leste's national ivermectin, diethylcarbamazine citrate, and albendazole MDA, for lymphatic filariasis elimination and soil-transmitted helminth (STH) control, on scabies, impetigo, and STH infections. METHODS: We did a before-after study in six primary schools across three municipalities in Timor-Leste (urban [Dili], semi-urban [Ermera], and rural [Manufahi]) before (April 23 to May 11, 2019) and 18 months after (Nov 9 to Nov 27, 2020) MDA delivery between May 17 and June 1, 2019. Study participants included schoolchildren, as well as infants, children, and adolescents who were incidentally present at school on study days. All schoolchildren whose parents provided consent were eligible to participate in the study. Infants, children, and adolescents younger than 19 years who were not enrolled in the school but were incidentally present at schools on study days were also eligible to participate if their parents consented. Ivermectin, diethylcarbamazine citrate, and albendazole MDA was implemented nationally, with single doses of oral ivermectin (200 µg/kg), diethylcarbamazine citrate (6 mg/kg), and albendazole (400 mg) administered by the Ministry of Health. Scabies and impetigo were assessed by clinical skin examinations, and STHs using quantitative PCR. The primary (cluster-level) analysis adjusted for clustering while the secondary (individual-level) analysis adjusted for sex, age, and clustering. The primary outcomes of the study were prevalence ratios for scabies, impetigo, and STHs (Trichuris trichiura, Ascaris lumbricoides, Necator americanus, and moderate-to-heavy A lumbricoides infections) between baseline and 18 months from the cluster-level analysis. FINDINGS: At baseline, 1043 (87·7%) of 1190 children registered for the study underwent clinical assessment for scabies and impetigo. The mean age of those who completed skin examinations was 9·4 years (SD 2·4) and 514 (53·8%) of 956 were female (87 participants with missing sex data were excluded from this percentage calculation). Stool samples were received for 541 (45·5%) of 1190 children. The mean age of those for whom stool samples were received was 9·8 years (SD 2·2) and 300 (55·5%) were female. At baseline, 348 (33·4%) of 1043 participants had scabies, and 18 months after MDA, 133 (11·1%) of 1196 participants had scabies (prevalence ratio 0·38, 95% CI 0·18-0·88; p=0·020) in the cluster-level analysis. At baseline, 130 (12·5%) of 1043 participants had impetigo, compared with 27 (2·3%) of 1196 participants at follow-up (prevalence ratio 0·14, 95% CI 0·07-0·27; p<0·0001). There was a significant reduction in T trichiura prevalence from baseline (26 [4·8%] of 541 participants) to 18-month follow-up (four [0·6%] of 623 participants; prevalence ratio 0·16, 95% CI 0·04-0·66; p<0·0001). In the individual-level analysis, moderate-to-heavy A lumbricoides infections reduced from 54 (10·0%; 95% CI 0·7-19·6) of 541 participants to 28 (4·5%, 1·2-8·4) of 623 participants (relative reduction 53·6%; 95% CI 9·1-98·1; p=0·018). INTERPRETATION: Ivermectin, diethylcarbamazine citrate, and albendazole MDA was associated with substantial reductions in prevalence of scabies, impetigo, and T trichiura, and of moderate-to-heavy intensity A lumbricoides infections. Combination MDA could be used to support integrated control programmes to target multiple NTDs. FUNDING: National Health and Medical Research Council of Australia and the Department of Foreign Affairs and Trade Indo-Pacific Centre for Health Security. TRANSLATION: For the Tetum translation of the abstract see Supplementary Materials section.

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.

Abbreviated Echocardiographic Screening for Rheumatic Heart Disease by Nonexperts with and without Offsite Expert Review: A Diagnostic Accuracy Study.

BACKGROUND: Early detection of rheumatic heart disease (RHD) through echocardiographic screening can facilitate early access to effective treatment, which reduces the risk for progression. Accurate, feasible approaches to echocardiographic screening that can be incorporated into routine health services are needed. The authors hypothesized that offsite expert review could improve the diagnostic accuracy of nonexpert-obtained echocardiographic images. METHODS: This prospective cross-sectional study was performed to evaluate the diagnostic accuracy of health worker-conducted single parasternal long-axis view with a sweep of the heart using hand-carried ultrasound for the detection of RHD in high-risk populations in Timor-Leste and Australia. In the primary analysis, the presence of any mitral or aortic regurgitation met the criteria for a positive screening result. Sensitivity and specificity were calculated for a screen-and-refer approach based on nonexpert practitioner assessment (approach 1) and for an approach using offsite expert review of nonexpert practitioner-obtained images to decide onward referral (approach 2). Each participant had a reference test performed by an expert echocardiographer on the same day as the index test. Diagnosis of RHD was determined by a panel of three experts, using 2012 World Heart Federation criteria. RESULTS: The prevalence of borderline or definite RHD among 3,329 participants was 4.0% (95% CI, 3.4%-4.7%). The sensitivity of approach 1 for borderline or definite RHD was 86.5% (95% CI, 79.5%-91.8%), and the specificity was 61.4% (95% CI, 59.7%-63.1%). Approach 2 achieved similar sensitivity (88.4%; 95% CI, 81.5%-93.3%) and improved specificity (77.1%; 95% CI, 75.6%-78.6%). CONCLUSION: Nonexpert practitioner-obtained single parasternal long-axis view with a sweep of the heart images, reviewed by an offsite expert, can detect borderline and definite RHD on screening with reasonable sensitivity and specificity. Brief training of nonexpert practitioners with ongoing support could be used as an effective strategy for scaling up echocardiographic screening for RHD in high-risk settings.

The COVID-19 laboratory response in Timor-Leste; a story of collaboration.

Timor-Leste is a small nation of 1.3 million people which shares a land border with Indonesia and is 550 km from Darwin, Australia. It is one of the poorest nations in Asia. The National Health Laboratory (NHL) and its network of smaller laboratories in Timor-Leste had limited capacity to perform molecular diagnostic testing before the coronavirus disease 2019 (COVID-19) pandemic began. With the support of international development partners, the NHL rapidly expanded its molecular testing service. From March 2020 to February 2022, over 200,000 molecular tests were performed; COVID-19 testing sites were established in hospital and community health center laboratories and all 13 municipalities, and the number of scientists and technicians at the molecular diagnostic laboratory at the NHL increased from five to 28 between 2019 and 2022. Molecular diagnostic testing for COVID-19 was successfully established at the NHL and in the municipalities. The molecular diagnostic laboratory at NHL is now equipped to respond to not only large-scale COVID-19 testing but also laboratory detection of other infectious diseases, preparing Timor-Leste for future outbreaks or pandemics.

The epidemiology of the COVID-19 pandemic in the small, low-resource country of Timor-Leste, January 2020 - June 2022.

Abstract: Timor-Leste, a small, mountainous half-island nation which shares a land border with Indonesia and which is 550 km from Australia, has a population of 1.3 million and achieved independence for the second time in 2002. It is one of the poorest nations in Asia. In response to the global coronavirus disease 2019 (COVID-19) pandemic, the Timor-Leste Ministry of Health undertook surveillance and contact tracing activities on all notified COVID-19 cases. Between 1 January 2020 and 30 June 2022, there were 22,957 cases of COVID-19 notified which occurred in three waves, the first which was delayed until April 2021 (community transmission of B.1.466.2 variant following major flooding), followed by waves in August 2021 (B.1.617.2 Delta variant transmission) and February 2022 (B.1.1.529 Omicron variant transmission). There were 753 people hospitalised due to COVID-19 and 133 deaths. Of the 133 deaths, 122 (92%) were considered not fully vaccinated (< 2 COVID-19 vaccines) and none had received boosters. Timor-Leste implemented measures to control COVID-19, including: rapid closure of international borders; isolation of cases; quarantining of international arrivals and close contacts; restrictions on internal travel; social and physical distancing; and, finally, a country-wide vaccination program. The health system's capacity was never exceeded.