Antimicrobial prescribing in referral hospitals in Timor-Leste: results of the first two national point prevalence surveys, 2020-21.

Objectives: To describe antimicrobial use (AMU) in patients admitted to hospitals in Timor-Leste. Methods: In 2020 and 2021, we undertook antimicrobial prescribing point prevalence surveys across all six hospitals in Timor-Leste (one national and five municipal) to describe AMU and appropriateness in admitted patients. Results: In 2020, 291/394 (73.9%) surveyed patients had been prescribed antimicrobials, compared with 260/403 (64.5%) in 2021 (P = 0.004). Most (309/551; 56.1%) were prescribed one antimicrobial, and 179/551 (32.5%) were prescribed two. The most commonly prescribed antibiotics were ceftriaxone (38.5% in 2020, 41.5% in 2021) and ampicillin (35.7% in 2020, 32.3% in 2021), followed by gentamicin, metronidazole and cloxacillin. Reserve antibiotics like meropenem and vancomycin were minimally used. Of all antimicrobial prescriptions, 70.8% were deemed appropriate in 2020 and 69.1% in 2021. Antimicrobial prescriptions for surgical and post-partum prophylaxis were frequently deemed inappropriate [37/50 (74.0%) and 39/44 (88.6%) prescriptions, respectively]. Conclusions: Most patients admitted to hospital in Timor-Leste are prescribed antimicrobials, and approximately one-third of these prescriptions are inappropriate. However, this was in the context of limited local guideline availability at the time of surveys and limited microbiological culture capacity outside of the capital, Dili. Improved microbiological guidance, iterative guideline revisions based on local antimicrobial resistance (AMR) surveillance data, and enhanced stewardship activities including further point prevalence studies, could improve antimicrobial use, optimize patient outcomes and reduce AMR in Timor-Leste.

Artificial intelligence in cardiac surgery: A systematic review.

BACKGROUND: Artificial intelligence (AI) has emerged as a tool to potentially increase the efficiency and efficacy of cardiovascular care and improve clinical outcomes. This study aims to provide an overview of applications of AI in cardiac surgery. METHODS: A systematic literature search on AI applications in cardiac surgery from inception to February 2024 was conducted. Articles were then filtered based on the inclusion and exclusion criteria and the risk of bias was assessed. Key findings were then summarized. RESULTS: A total of 81 studies were found that reported on AI applications in cardiac surgery. There is a rapid rise in studies since 2020. The most popular machine learning technique was random forest (n = 48), followed by support vector machine (n = 33), logistic regression (n = 32), and eXtreme Gradient Boosting (n = 31). Most of the studies were on adult patients, conducted in China, and involved procedures such as valvular surgery (24.7%), heart transplant (9.4%), coronary revascularization (11.8%), congenital heart disease surgery (3.5%), and aortic dissection repair (2.4%). Regarding evaluation outcomes, 35 studies examined the performance, 26 studies examined clinician outcomes, and 20 studies examined patient outcomes. CONCLUSION: AI was mainly used to predict complications following cardiac surgeries and improve clinicians' decision-making by providing better preoperative risk assessment, stratification, and prognostication. While the application of AI in cardiac surgery has greatly progressed in the last decade, further studies need to be conducted to verify accuracy and ensure safety before use in clinical practice.

The first confirmed human case of rabies, Timor-Leste, 2024.

In March 2024, the first ever human case of rabies, following a dog bite, was detected in Timor-Leste. This paper briefly discusses the circumstances of transmission, clinical presentation, palliative care of the case and public health measures taken. Timor-Leste was previously considered rabies-free. Any person who is bitten or scratched by an animal that could potentially transmit rabies virus (especially dogs, bats, monkeys or cats) in Timor-Leste should be assessed for consideration of provision of rabies post-exposure prophylaxis.

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.

Efficacy of delayed pegfilgrastim administration following consolidation therapy with high-dose cytarabine (HiDAC) in acute myeloid leukemia (AML) patients.

PURPOSE: To study the effects of delaying pegfilgrastim administration following high-dose cytarabine (HiDAC) consolidation in AML patients on time to neutrophil count recovery, infectious complications, and survival. METHODS: Single-center retrospective chart review of 55 patients receiving pegfilgrastim as early administration (within 72 h) or delayed administration (after 72 h) of HiDAC. RESULTS: The difference in neutrophil recovery time was similar between the early and delayed groups (18 days versus 19 days, p < 0.28). Infections were seen in four patients in the early administration group following chemotherapy compared to none in the delayed group (p = 0.04). Febrile neutropenia rates were also decreased in the delayed administration group (23.1% versus 10.3%, p = 0.28) as well as a trend towards longer median survival (16 months versus 19 months, p = 0.69) and overall survival (21 months versus 31 months, p = 0.47). CONCLUSION: A difference in time to neutrophil recovery was not observed between the early and delayed administration groups yet decreased infectious complications may support the delayed administration of pegfilgrastim in these patients.

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.

Echocardiographic Screening for Rheumatic Heart Disease: A Brief History and Implications for the Future.

Transthoracic echocardiography is the gold standard for early detection of rheumatic heart disease (RHD) in asymptomatic children living in high-risk regions. Advances in technology allowing miniaturisation and increased portability of echocardiography devices have improved the accessibility of this vital diagnostic tool in RHD-endemic locations. Automation of image optimisation techniques and simplified RHD screening protocols permit use by non-experts after a brief period of training. While these changes are welcome advances in the battle to manage RHD, it is important that the sensitivity and specificity of RHD detection be maintained by all echocardiography users on any device to ensure accurate and timely diagnosis of RHD to facilitate initiation of appropriate therapy. This review of the evolution of echocardiography and its use in the detection of rheumatic valve disease may serve as a reminder of the key strengths and potential pitfalls of this increasingly relied-upon diagnostic test.

"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.

A pilot study using hospital surveillance and a birth cohort to investigate enteric pathogens and malnutrition in children, Dili, Timor-Leste.

In low-to-middle-income countries (LMICs), enteric pathogens contribute to child malnutrition, affecting nutrient absorption, inducing inflammation, and causing diarrhoea. This is a substantial problem in LMICs due to high disease burden, poor sanitation and nutritional status, and the cyclical nature of pathogen infection and malnutrition. This relationship remains understudied in Timor-Leste. In our pilot study of enteric pathogens and malnutrition in Dili, Timor-Leste (July 2019-October 2020), we recruited 60 infants in a birth cohort from Hospital Nacional Guido Valadares (HNGV) with up to four home visits. We collected faecal samples and details of demographics, anthropometrics, diet and food practices, and animal husbandry. Additionally, we collected faecal samples, diagnostics, and anthropometrics from 160 children admitted to HNGV with a clinical diagnosis of severe diarrhoea or severe acute malnutrition (SAM). We tested faeces using the BioFire® FilmArray® Gastrointestinal Panel. We detected high prevalence of enteric pathogens in 68.8% (95%CI 60.4-76.2%) of infants at home, 88.6% of SAM cases (95%CI 81.7-93.3%) and 93.8% of severe diarrhoea cases (95%CI 67.7-99.7%). Diarrhoeagenic Escherichia coli and Campylobacter spp. were most frequently detected. Pathogen presence did not significantly differ in birth cohort diarrhoeal stool, but hospital data indicated associations between Salmonella and Shigella and diarrhoea. We observed wasting in 18.4% (95%CI 9.2-32.5%) to 30.8% (95%CI 17.5-47.7%) of infants across home visits, 57.9% (95%CI 34.0-78.9%) of severe diarrhoea cases, and 92.5% (95%CI 86.4-96.2%) of SAM cases. We associated bottle feeding with increased odds of pathogen detection when compared with exclusive breastfeeding at home (OR 8.3, 95%CI 1.1-62.7). We detected high prevalence of enteric pathogens and signs of malnutrition in children in Dili. Our pilot is proof of concept for a study to fully explore the risk factors and associations between enteric pathogens and malnutrition in Timor-Leste.

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.

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.

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.

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.

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].

Corrigendum to "Lower risk of multi-system Inflammatory Syndrome in Children (MIS-C) with the Omicron variant" [The Lancet Regional Health - Western Pacific 27 (2022) 100604].

[This corrects the article DOI: 10.1016/j.lanwpc.2022.100604.].

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.