Characterization of gram-negative bloodstream infections in hospitalised Australian children and their clinical outcomes.

BACKGROUND: Gram-negative bloodstream infections (GNBSI) more commonly occur in children with comorbidities and are increasingly associated with antimicrobial resistance. There are few large studies of GNBSI in children that relate the clinical presentation, pathogen characteristics and outcomes. METHODS: A 3-year prospective study of GNBSI in children aged <18 years was conducted in five Australian children's hospitals between 2019-2021. The clinical characteristics, disease severity and outcomes were recorded. Causative pathogens underwent antibiotic susceptibility testing and whole genome sequencing. RESULTS: There were 931 GNBSI episodes involving 818 children. Median age was 3 years (IQR 0.6-8.5). 576/931 episodes (62%) were community onset though 661/931 (71%) occurred in children with comorbidities and a central venous catheter (CVC) was present in 558/931 (60%). CVC (145/931) and urinary tract (149/931) were the most common sources (16% each). 100/931 (11%) children required Intensive Care Unit (ICU) admission and a further 11% (105/931) developed GNBSI in ICU. 659/927 (71%) isolates were Enterobacterales of which 22% (138/630) were third generation cephalosporin resistant (3GCR). Extended spectrum beta-lactamase genes (ESBL) were confirmed in 65/138 (47%) 3GCR-Enterobacterales. Most common ESBL genes were blaCTX-M-15 (34/94, 36%) and blaSHV-12 (10/94, 11%). There were 48 deaths overall and 30-day in-hospital mortality was 3% (32/931). Infections with 3GCR Enterobacterales were independently associated with higher mortality (adjusted OR 3.2, 95%CI 1.6-6.4). CONCLUSION: GNBSI in children are frequently healthcare-associated and affect children under 5 years. Infections with 3GCR Enterobacterales were associated with worse outcomes. These findings will inform optimal management guidelines and help prioritise future antimicrobial clinical trials.

Onward Virus Transmission after Measles Secondary Vaccination Failure.

Measles in persons with secondary vaccination failure (SVF) may be less infectious than cases in unvaccinated persons. Our systematic review aimed to assess transmission risk for measles after SVF. We searched PubMed, Embase, and Web of Science databases from their inception dates. Inclusion criteria were articles describing persons who were exposed to measles-infected persons who had experienced SVF. Across the included 14 studies, >3,030 persons were exposed to measles virus from SVF cases, of whom 180 were susceptible, indicating secondary attack rates of 0%-6.25%. We identified 109 cases of SVF from the studies; 10.09% (n = 11) of case-patients transmitted the virus, resulting in 23 further cases and yielding an effective reproduction number of 0.063 (95% CI 0.0-0.5). These findings suggest a remarkably low attack rate for SVF measles cases, suggesting that, In outbreak situations, public health management of unvaccinated persons could be prioritized over persons with SVF.

The provision of sexual and reproductive health information and services to travellers: an exploratory survey of Australian travel medicine clinicians.

BACKGROUND: International travel can increase the risk of exposure to infectious diseases including sexually transmissible infections (STI). Pre-travel medical consultation provides an opportunity for travel-related health risk assessments and advice. This study explored how travel medicine clinicians integrate sexual and reproductive health (SRH) services into clinical practice. METHODS: A convenience sample of travel medicine clinicians completed a cross-sectional survey online or via hard-copy disseminated at an annual national Australian travel medicine conference. RESULTS: Of the 67 respondents, most (n , 51; 76.1%) had a postgraduate qualification relevant to travel medicine and 55.2% (n , 37) had worked in travel medicine for over 10years. Only 22.4% (n , 15) reported conducting a SRH history/STI risk assessment for all travel patients. STI testing pre-departure was conducted on patient request (48, 71.6%), if symptomatic (32, 47.8%) or based on risk history (28, 41.8%). SRH information pre-departure was most frequently provided if prompted by patient questions (n , 42; 62.7%), or based on the patient's history (n , 37; 55.2%). Over half the sample (n , 40; 59.7%) expressed interest in further training in SRH. CONCLUSION: Providing and engaging with additional training may assist travel medicine clinicians to take a more proactive approach to SRH consultations and STI testing. Additional research is needed to explore models of care that will allow comprehensive SRH and STI services to be integrated into standard pre- and post-travel care.

Remembering Professor Peter A. Leggat, AM, ADC (1961-2023).

Professor Peter Leggat, the Immediate Past President of the Australasian College of Tropical Medicine (ACTM), passed away peacefully in Brisbane on 20 September 2023 [...].

Mastering geographically weighted regression: key considerations for building a robust model.

Geographically weighted regression (GWR) takes a prominent role in spatial regression analysis, providing a nuanced perspective on the intricate interplay of variables within geographical landscapes (Brunsdon et al., 1998). However, it is essential to have a strong rationale for employing GWR, either as an addition to, or a complementary analysis alongside, non-spatial (global) regression models (Kiani, Mamiya et al., 2023). Moreover, the proper selection of bandwidth, weighting function or kernel types, and variable choices constitute the most critical configurations in GWR analysis (Wheeler, 2021). [...].

Operational research to inform post-validation surveillance of lymphatic filariasis in Tonga study protocol: History of lymphatic filariasis elimination, rational, objectives, and design.

BACKGROUND: Lymphatic filariasis (LF), a mosquito-borne helminth infection, is an important cause of chronic disability globally. The World Health Organization has validated eight Pacific Island countries as having eliminated lymphatic filariasis (LF) as a public health problem, but there are limited data to support an evidence-based approach to post-validation surveillance (PVS). Tonga was validated as having eliminated LF in 2017 but no surveillance has been conducted since 2015. This paper describes a protocol for an operational research project investigating different PVS methods in Tonga to provide an evidence base for national and regional PVS strategies. METHODS: Programmatic baseline surveys and Transmission Assessment Surveys conducted between 2000-2015 were reviewed to identify historically 'high-risk' and 'low-risk' schools and communities. 'High-risk' were those with LF antigen (Ag)-positive individuals recorded in more than one survey, whilst 'low-risk' were those with no recorded Ag-positives. The outcome measure for ongoing LF transmission will be Ag-positivity, diagnosed using Alere™ Filariasis Test Strips. A targeted study will be conducted in May-July 2024 including: (i) high and low-risk schools and communities, (ii) boarding schools, and (iii) patients attending a chronic-disease clinic. We estimate a total sample size of 2,010 participants. CONCLUSIONS: Our methodology for targeted surveillance of suspected 'high-risk' populations using historical survey data can be adopted by countries when designing their PVS strategies. The results of this study will allow us to understand the current status of LF in Tonga and will be used to develop the next phase of activities.

Post-marketing surveillance of 10,392 herpes zoster vaccines doses in Australia.

BACKGROUND: Immunisation against herpes zoster is recommended for adults aged ≥ 50 years. Two vaccines, a live attenuated (ZVL, Zostavax®) and an adjuvant recombinant subunit (HZ/su, Shingrix®), are available in Australia. Immunisation guidelines are shifting their recommendations towards HZ/su because of higher efficacy in preventing herpes zoster and associated complications. However, there are limited post-marketing data comparing the safety profiles of these vaccines. METHODS: Data from SmartVax, an active surveillance system for monitoring adverse events following immunisation (AEFIs) utilised by > 450 clinics throughout Australia, were analysed. Data from patients aged ≥ 50 years, who received ZVL or HZ/su, from 1 June 2021 to 31 May 2022, at clinics that utilised SmartVax were included. The proportion of records where patients who reported any, local, and systemic AEFIs after receiving ZVL or HZ/su were compared using multivariable logistic regression models. RESULTS: Data from 10,392 immunisation records (n = 8341 ZVL; n = 2051 HZ/su) were included. The proportion of AEFIs reported was higher with HZ/su (41.9 % [any], 33.8 % [local], 25.2 % [systemic]) than with ZVL (8.7 % [any], 6.2 % [local], 3.5 % [systemic]). After controlling for demographic variables, HZ/su presented a 6-fold increase in the odds (OR 6.44; 95 %CI: 5.57-7.46) of a reported AEFI compared to ZVL. Only 59 (0.6 %) of vaccinations lead to medical attention being sought due to an AEFI. CONCLUSIONS: While rates of AEFIs was higher with HZ/su than ZVL, most AEFIs were mild and did not require medical attention. Our findings support the change in vaccine recommendations and the use of HZ/su in immunisation programs.

Malaria cases in China acquired through international travel, 2013-2022.

BACKGROUND: Despite the World Health Organisation certifying China malaria-free in 2021, the risk of local transmission caused by imported malaria cases remains a significant clinical and public health issue. It is necessary to present the changing trends of malaria in China and discuss the role of travel medicine services in consolidating malaria elimination. METHODS: This study systematically reviewed articles and reports related to human malaria from 2013 to 2022 published in international and Chinese databases. Data on malaria (i.e. number of cases, Plasmodium spp., diagnostic method, country of acquisition, provinces with high risk of re-introduction and transmission) were collected and synthesised, then summarised using descriptive statistics. RESULTS: Overall, 24 758 cases of malaria (>99.5% laboratory confirmed, > 99.2% imported, 0.5% fatal) were reported in China from 2013 to 2022, with a downward trend over the years (4128 cases in 2013 compared to 843 cases in 2022; χ2 trend p-value = 0.005). The last locally acquired case was reported in 2017. P. falciparum (65.5%) was the most common species identified, followed by P. vivax (20.9%) and P. ovale (10.0%). Two Pheidole knowlesi cases were also identified in 2014 and 2017 in returned travellers from Malaysia and Indonesia, respectively. The most common countries of malaria acquisition were Ghana, Angola, and Myanmar. P. vivax was mainly detected in returned travellers from Myanmar, while P. falciparum and P. ovale were detected in travellers from Sub-Saharan Africa. Imported cases were mainly reported in Yunnan, Jiangsu, Sichuan, Guangxi, Shandong, Zhejiang, and Henan provinces, where large numbers of Chinese people travel overseas for work. CONCLUSION: Returned travellers from malaria-endemic countries pose a significant risk of malaria re-introduction to China. Travel medicine should be strengthened to improve the capacity and accessibility of both pre- and post-travel services, including malaria prophylaxis and prompt diagnosis of illness in returned travellers.

Ongoing transmission of lymphatic filariasis in Samoa 4.5 years after one round of triple-drug mass drug administration.

BACKGROUND: Lymphatic filariasis (LF) remains a significant global issue. To eliminate LF as a public health problem, the World Health Organization (WHO) recommends multiple rounds of mass drug administration (MDA). In certain scenarios, including when elimination targets have not been met with two-drug MDA, triple-drug MDA (using ivermectin, diethylcarbamazine and albendazole) is recommended. In this study, we report on antigen (Ag) and microfilaria (Mf) prevalence in eight primary sampling units (PSUs) in Samoa 4.5 years after one round of triple-drug MDA. METHODOLOGY: In 2023, community surveys were conducted in eight PSUs that had been surveyed previously in 2018 (between 1.5 and 3.5 months post triple-drug MDA) and 2019 (six to eight-months post triple-drug MDA). Fifteen houses were randomly selected in each PSU with household members aged ≥ 5 years invited to participate. Blood samples were tested for Ag and Mf. PRINCIPAL FINDINGS: Ag-positive participants were observed in six of the eight PSUs, and Ag prevalence was significantly above the 1% threshold in four PSUs. The presence of Mf-positive participants in five PSUs confirms the presence of residual active infections. CONCLUSIONS/SIGNIFICANCE: This study provides evidence of persistent LF transmission in Samoa 4.5 years after one round of triple-drug MDA, confirming that one round was insufficient for interruption of transmission in this setting. Our findings highlight the negative impact of delaying MDA rounds, for example, due to public health emergencies.

A systematic review and meta-analysis of sexually transmitted infections and blood-borne viruses in travellers.

BACKGROUND: Sexually transmitted infections (STIs) and blood-borne viruses (BBVs) impose a global health and economic burden. International travellers facilitate the spread of infectious diseases, including STIs. Hence, this review assessed the prevalence/proportionate morbidity of travellers with STIs and sexually transmitted BBVs and factors associated with the infection in this population. METHODS: PubMed, Scopus, Web of Science, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Embase and Cochrane Library were searched from inception of the databases until November 2022. Published analytical observational studies reporting the prevalence/proportionate morbidity of travellers with STIs and factors associated with STIs by type of traveller [i.e. tourists, business travellers, students, visiting friends or relatives (VFRs), international truck drivers, backpackers, expatriates and men who have sex with men (MSM)] were included. The selection of articles, data extraction and risk of bias assessment were conducted by two independent reviewers. Meta-analyses were conducted for each STI by clinical presentation and type of traveller. RESULTS: Thirty-two studies (n = 387 731 travellers) were included; 19 evaluated the proportionate morbidity of STIs among symptomatic travellers, while 13 examined the prevalence of STIs in asymptomatic travellers. The highest proportionate morbidity was found among VFRs (syphilis, 1.67%; 95% CI: 1.03-2.81%), backpackers (Chlamydia trachomatis, 6.58%; 95% CI: 5.96-7.25%) and MSM (HIV [2.50%;95% CI: 0.44-12.88%], gonorrhoea [4.17%; 95% CI: 1.1.5-13.98%], lymphogranuloma venereum [4.17%;95% CI: 1.1.5-13.98%] and HAV [20.0%; 95% CI: 14.99-26.17%]). The highest prevalence of STIs among asymptomatic were found in MSM (HIV [25.94%; 95% CI: 22.21-30.05%] and HBV [24.90%; 95% CI: 21.23-28.96%]) and backpackers (C. trachomatis, 3.92%; 95% CI: 2.72-5.32%). Short duration of the trip (<1 month), not having pre-travel consultation, travelling to Southeast Asia and being unvaccinated for HBV were identified as risk factors for STIs. CONCLUSION: Strategies to prevent STIs and sexually transmitted BBVs should be discussed at pre-travel consultations, and recommendations should be prioritized in high-risk groups of travellers, such as backpackers, VFRs and MSMs. Additionally, healthcare providers should tailor recommendations for safe sex practices to individual travellers' unique needs.

Anti-filarial antibodies are sensitive indicators of lymphatic filariasis transmission and enable identification of high-risk populations and hotspots.

OBJECTIVES: Circulating filarial antigen (Ag) is used by elimination programs to monitor lymphatic filariasis (LF) transmission; however, antifilarial antibodies (Ab) may be more sensitive than Ag for detecting LF. Our objectives were to describe Ab seroprevalence, identify risk factors for Ab seropositivity, investigate age-specific associations between Ag and Ab, and evaluate geographic clustering of seropositivity. METHODS: Community-based serosurveys of participants aged ≥5 years were conducted in 35 primary sampling units (PSUs). Ag-positivity was detected using Alere™ Filariasis Test Strips and Ab-seropositivity using multiplex bead assays. Seroprevalence was adjusted for study design. RESULTS: Of 3795 participants (range:5-90 years), adjusted prevalence for Ag, Bm14 Ab, Wb123 Ab, and Bm33 Ab were 3.7% (n=117), 20.3% (n=583), 32.2% (n=987), and 51.0% (n=1659), respectively. Male sex, older age, and residents of suspected hotspots had higher odds of seropositivity to all seromarkers. Seroprevalence was lower in 5-9-year-olds vs ≥10-year-olds (p<0.001). Clustering was significantly higher in households (intra-cluster correlation for Ag:0.45; Bm14 Ab:0.32; Bm33 Ab:0.31; Wb123 Ab:0.29) compared to PSUs or region. CONCLUSIONS: Abs enabled identification of risk factors for seropositivity and geographical clustering to inform targeted interventions for LF programmes. Further research is needed to define Ab thresholds for active versus past infection and elimination targets.

Protocol for spatial prediction of soil transmitted helminth prevalence in the Western Pacific region using a meta-analytical approach.

BACKGROUND: Soil transmitted helminth (STH) infections are estimated to impact 24% of the world's population and are responsible for chronic and debilitating morbidity. Disadvantaged communities are among the worst affected and are further marginalized as infection prevalence fuels the poverty cycle. Ambitious targets have been set to eliminate STH infections, but accurate epidemiological data will be required to inform appropriate interventions. This paper details the protocol for an analysis that aims to produce spatial prediction mapping of STH prevalence in the Western Pacific Region (WPR). METHODS: The protocol follows the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocol (PRISMA-P) guidelines. The study design will combine the principles of systematic review, meta-analysis, and geospatial analysis. Systematic searches will be undertaken in PubMed, Scopus, ProQuest, Embase, and Web of Science for studies undertaken post 2000, to identify surveys that enable the prevalence of human STH infection within the WPR to be calculated. Covariate data for multivariable analysis will be obtained from publicly accessible sources. Survey data will be geolocated, and STH prevalence and covariates will be linked to produce a spatially referenced dataset for analysis. Bayesian model-based geostatistics will be used to generate spatially continuous estimates of STH prevalence mapped to a resolution of 1 km2. A separate geospatial model will be constructed for each STH species. Predictions of prevalence will be made for unsampled locations and maps will be overlaid for each STH species to obtain co-endemicity maps. DISCUSSION: This protocol facilitates study replication and may be applied to other infectious diseases or alternate geographies. Results of the subsequent analysis will identify geographies with high STH prevalence's and can be used to inform resource allocation in combating this neglected tropical disease. TRIAL REGISTRATION: Open Science Framework: osf.io/qmxcj.

Suppression of adaptive NK cell expansion by macrophage-mediated phagocytosis inhibited by 2B4-CD48.

Infection of mice by mouse cytomegalovirus (MCMV) triggers activation and expansion of Ly49H+ natural killer (NK) cells, which are virus specific and considered to be "adaptive" or "memory" NK cells. Here, we find that signaling lymphocytic activation molecule family receptors (SFRs), a group of hematopoietic cell-restricted receptors, are essential for the expansion of Ly49H+ NK cells after MCMV infection. This activity is largely mediated by CD48, an SFR broadly expressed on NK cells and displaying augmented expression after MCMV infection. It is also dependent on the CD48 counter-receptor, 2B4, expressed on host macrophages. The 2B4-CD48 axis promotes expansion of Ly49H+ NK cells by repressing their phagocytosis by virus-activated macrophages through inhibition of the pro-phagocytic integrin lymphocyte function-associated antigen-1 (LFA-1) on macrophages. These data identify key roles of macrophages and the 2B4-CD48 pathway in controlling the expansion of adaptive NK cells following MCMV infection. Stimulation of the 2B4-CD48 axis may be helpful in enhancing adaptive NK cell responses for therapeutic purposes.

Imported malaria into Australia: surveillance insights and opportunities.

BACKGROUND: Malaria continues to pose a significant burden in endemic countries, many of which lack access to molecular surveillance. Insights from malaria cases in travellers returning to non-endemic areas can provide valuable data to inform endemic country programmes. To evaluate the potential for novel global insights into malaria, we examined epidemiological and molecular data from imported malaria cases to Australia. METHODS: We analysed malaria cases reported in Australia from 2012 to 2022 using National Notifiable Disease Surveillance System data. Molecular data on imported malaria cases were obtained from literature searches. RESULTS: Between 2012 and 2022, 3204 malaria cases were reported in Australia. Most cases (69%) were male and 44% occurred in young adults aged 20-39 years. Incidence rates initially declined between 2012 and 2015, then increased until 2019. During 2012-2019, the incidence in travellers ranged from 1.34 to 7.71 per 100 000 trips. Cases were primarily acquired in Sub-Saharan Africa (n = 1433; 45%), Oceania (n = 569; 18%) and Southern and Central Asia (n = 367; 12%). The most common countries of acquisition were Papua New Guinea (n = 474) and India (n = 277). Plasmodium falciparum accounted for 58% (1871/3204) of cases and was predominantly acquired in Sub-Saharan Africa, and Plasmodium vivax accounted for 32% (1016/3204), predominantly from Oceania and Asia. Molecular studies of imported malaria cases to Australia identified genetic mutations and deletions associated with drug resistance and false-negative rapid diagnostic test results, and led to the establishment of reference genomes for P. vivax and Plasmodium malariae. CONCLUSIONS: Our analysis highlights the continuing burden of imported malaria into Australia. Molecular studies have offered valuable insights into drug resistance and diagnostic limitations, and established reference genomes. Integrating molecular data into national surveillance systems could provide important infectious disease intelligence to optimize treatment guidelines for returning travellers and support endemic country surveillance programmes.

Integrating sexual and reproductive health into pre-travel consultations.

BACKGROUND: Casual sex during travel is a major preventable factor in the global transmission of sexually transmissible infections (STI). Pre-travel consults present an excellent opportunity for practitioners to educate travellers about sexual and reproductive health (SRH) and safety. This scoping review aims to explore and understand the extent to which SRH is included in pre-travel consultations. METHODS: PubMed, Embase, Cumulative Index to Nursing and Allied Health Literature, Scopus, Medline and Web of Science were systematically searched for primary research articles exploring whether health care practitioners (HCP) included SRH in pre-travel consultations. Extracted findings were synthesized and presented in narrative form. RESULTS: Findings across 13 articles suggest HCPs infrequently broached SRH in pre-travel consultations with HCP discomfort, and lack of time and resources presented as key barriers. Urban practice settings, HCP experience, training in travel medicine and traveller characteristics such as sexual orientation were positively associated with discussions about SRH. SRH advice reported was general in nature, primarily focusing on safer sex, condoms or unspecified STI advice. Risk assessments based solely on age or stereotypes around sexual preferences led to key aspects of SRH care being missed for some (e.g. SRH was less likely to be discussed with older travellers). CONCLUSIONS: HCPs frequently miss opportunities to integrate SRH into pre-travel consultations. Strategies to promote HCP confidence and awareness present a promising means to boost the frequency and quality of SRH advice disseminated. Integrating culturally safe and responsive SRH history-taking and advice into pre-travel consultations may contribute to global reductions in STI transmission and promote traveller SRH well-being.

Field laboratory comparison of STANDARD Q Filariasis Antigen Test (QFAT) with Bioline Filariasis Test Strip (FTS) for the detection of Lymphatic Filariasis in Samoa, 2023.

BACKGROUND: To monitor the progress of lymphatic filariasis (LF) elimination programmes, field surveys to assess filarial antigen (Ag) prevalence require access to reliable, user-friendly rapid diagnostic tests. We aimed to evaluate the performance of the new Q Filariasis Antigen Test (QFAT) with the currently recommended Filariasis Test Strip (FTS) for detecting the Ag of Wuchereria bancrofti, the causative agent of LF, under field laboratory conditions. METHODOLOGY/PRINCIPAL FINDINGS: During an LF survey in Samoa, 344 finger-prick blood samples were tested using FTS and QFAT. Microfilariae (Mf) status was determined from blood slides prepared from any sample that reported Ag-positive by either Ag-test. Each test was re-read at 1 hour and the next day to determine the stability of results over time. Overall Ag-positivity by FTS was 29.0% and 30.2% by QFAT. Concordance between the two tests was 93.6% (kappa = 0.85). Of the 101 Mf slides available, 39.6% were Mf-positive, and all were Ag-positive by both tests. Darker test line intensities from Ag-positive FTS were found to predict Mf-positivity (compared to same/lighter line intensities). QFAT had significantly higher reported test result changes than FTS, mostly reported the next day, but fewer changes were reported between 10 minutes to 1hour. The field laboratory team preferred QFAT over FTS due to the smaller blood volume required, better usability, and easier readability. CONCLUSION/SIGNIFICANCE: QFAT could be a suitable and user-friendly diagnostic alternative for use in the monitoring and surveillance of LF in field surveys based on its similar performance to FTS under field laboratory conditions.

Risk mapping and socio-ecological drivers of soil-transmitted helminth infections in the Philippines: a spatial modelling study.

Background: The Philippines reports a high prevalence of soil-transmitted helminth (STH) infections despite the implementation of nationwide mass drug administration since 2006. The spatial variation of STH infections in the Philippines was last described using the 2005-2007 national STH and schistosomiasis survey. This study aimed to identify sociodemographic and environmental factors that drive STH transmission and predict high-risk areas in the Philippines. Methods: Epidemiological data on STH for students aged 5-16 years were obtained from the 2015 Philippines National Prevalence survey, while environmental data were extracted from satellite images and publicly available sources. Model-based geostatistics, implemented in a Bayesian framework, was used to identify sociodemographic and environmental correlates and predict high-risk areas for STH across the Philippines. The best-fitting model with the lowest deviance information criterion (DIC) was used to interpret the findings of the model and predict STH infection risk for the entire country. Risk maps were developed for each STH infection using the posterior means derived from the model. Findings: The prevalence of Ascaris lumbricoides (20.0%) and Trichuris trichiura (29.3%) was higher in the Visayas Island than in the Luzon and Mindanao Islands. Hookworm prevalence was highest in Mindanao Island (1.3%). Risk of A. lumbricoides was positively associated with males (odds ratio [OR]: 1.197; 97.5% Credible Interval [CrI]: 1.114, 1.286) and temperature (OR: 1.148; 97.5% CrI: 1.033, 1.291), while normalized difference vegetation index (OR: 0.354; 97.5% CrI: 0.138, 0.930) and soil pH (OR: 0.606; 97.5% CrI: 0.338, 0.949) were negatively associated with the transmission. T. trichiura risk was positively associated with males (OR: 1.261; 97.5% CrI: 1.173, 1.341), temperature (OR: 1.153; 97.5% CrI: 1.001, 1.301), and rainfall (OR: 1.004; 97.5% CrI: 1.011, 1.069). Hookworm risk was positively associated with males (OR: 2.142; 97.5% CrI: 1.537, 2.998), while children aged ≤12 years (OR: 0.435; 97.5% CrI: 0.252, 0.753) had a negative association with risk compared to those over 12 years. Focal areas of high risk were identified for A. lumbricoides and T. trichiura in the Visayas Island, and hookworm in the Mindanao Island. Interpretation: The spatial distribution of all three STH infections has considerably decreased since a previous national risk-mapping exercise. The high-risk areas identified in the study can be used to strategically target deworming and health education activities to further reduce the burden of STH and support progress toward elimination. Funding: The Australian Centre for the Control and Elimination of Neglected Tropical Diseases and the Australian National Health and Medical Research Council.

Trust and COVID-19 vaccine hesitancy in the Dominican Republic: a national cross-sectional household survey, June-October 2021.

OBJECTIVE: This study investigates the role of trust in shaping COVID-19 vaccine acceptance in the Dominican Republic (DR) during the COVID-19 pandemic. DESIGN: Cross-sectional household survey. SETTING: Randomly selected households across 134 clusters in the DR, from 30 June 2021 to 12 October 2021. PARTICIPANTS: 5999 participants ≥16 years of age were enrolled. OUTCOME MEASURES: COVID-19 vaccine hesitancy (CVH) data were collected from participants ≥16 years of age and analysed as both an ordinal and binary variable. RESULTS: Overall, CVH was low (5.2% (95% CI 4.6% to 5.8%)), but more common among younger individuals, women and individuals of Mestizo ethnicity. Higher trust in local government, national government, scientists and local doctors (considered official sources) was associated with lower odds of CVH (OR 0.89 (95% CI 0.72 to 0.88), 0.89 (95% CI 0.81 to 0.98), 0.87 (95% CI 0.80 to 0.94) and 0.70 (95% CI 0.62 to 0.80), respectively). Higher trust in religious leaders, social media and traditional media (considered unofficial sources) was associated with higher odds of CVH, with respective ORs of 1.32 (95% CI 1.18 to 1.47), 1.30 (95% CI 1.19 to 1.41) and 1.08 (95% CI 0.97 to 1.22). CONCLUSION: We report findings on CVH from a national household survey in the DR and identify overall low rates of CVH but marked heterogeneity by age, gender and ethnicity. Trust in unofficial versus official sources of information is associated with increased CVH. These findings highlight and quantify the importance of trust as a key parameter when considering public health communication strategies.

Genome-wide screening identifies Trim33 as an essential regulator of dendritic cell differentiation.

The development of dendritic cells (DCs), including antigen-presenting conventional DCs (cDCs) and cytokine-producing plasmacytoid DCs (pDCs), is controlled by the growth factor Flt3 ligand (Flt3L) and its receptor Flt3. We genetically dissected Flt3L-driven DC differentiation using CRISPR-Cas9-based screening. Genome-wide screening identified multiple regulators of DC differentiation including subunits of TSC and GATOR1 complexes, which restricted progenitor growth but enabled DC differentiation by inhibiting mTOR signaling. An orthogonal screen identified the transcriptional repressor Trim33 (TIF-1γ) as a regulator of DC differentiation. Conditional targeting in vivo revealed an essential role of Trim33 in the development of all DCs, but not of monocytes or granulocytes. In particular, deletion of Trim33 caused rapid loss of DC progenitors, pDCs, and the cross-presenting cDC1 subset. Trim33-deficient Flt3+ progenitors up-regulated pro-inflammatory and macrophage-specific genes but failed to induce the DC differentiation program. Collectively, these data elucidate mechanisms that control Flt3L-driven differentiation of the entire DC lineage and identify Trim33 as its essential regulator.