Spatio-temporal spread of artemisinin resistance in Southeast Asia.

Current malaria elimination targets must withstand a colossal challenge-resistance to the current gold standard antimalarial drug, namely artemisinin derivatives. If artemisinin resistance significantly expands to Africa or India, cases and malaria-related deaths are set to increase substantially. Spatial information on the changing levels of artemisinin resistance in Southeast Asia is therefore critical for health organisations to prioritise malaria control measures, but available data on artemisinin resistance are sparse. We use a comprehensive database from the WorldWide Antimalarial Resistance Network on the prevalence of non-synonymous mutations in the Kelch 13 (K13) gene, which are known to be associated with artemisinin resistance, and a Bayesian geostatistical model to produce spatio-temporal predictions of artemisinin resistance. Our maps of estimated prevalence show an expansion of the K13 mutation across the Greater Mekong Subregion from 2000 to 2022. Moreover, the period between 2010 and 2015 demonstrated the most spatial change across the region. Our model and maps provide important insights into the spatial and temporal trends of artemisinin resistance in a way that is not possible using data alone, thereby enabling improved spatial decision support systems on an unprecedented fine-scale spatial resolution. By predicting for the first time spatio-temporal patterns and extents of artemisinin resistance at the subcontinent level, this study provides critical information for supporting malaria elimination goals in Southeast Asia.

COVID-19 vaccine coverage targets to inform reopening plans in a low incidence setting.

Since the emergence of SARS-CoV-2 in 2019 through to mid-2021, much of the Australian population lived in a COVID-19-free environment. This followed the broadly successful implementation of a strong suppression strategy, including international border closures. With the availability of COVID-19 vaccines in early 2021, the national government sought to transition from a state of minimal incidence and strong suppression activities to one of high vaccine coverage and reduced restrictions but with still-manageable transmission. This transition is articulated in the national 're-opening' plan released in July 2021. Here, we report on the dynamic modelling study that directly informed policies within the national re-opening plan including the identification of priority age groups for vaccination, target vaccine coverage thresholds and the anticipated requirements for continued public health measures-assuming circulation of the Delta SARS-CoV-2 variant. Our findings demonstrated that adult vaccine coverage needed to be at least 60% to minimize public health and clinical impacts following the establishment of community transmission. They also supported the need for continued application of test-trace-isolate-quarantine and social measures during the vaccine roll-out phase and beyond.

Comparison of new computational methods for spatial modelling of malaria.

BACKGROUND: Geostatistical analysis of health data is increasingly used to model spatial variation in malaria prevalence, burden, and other metrics. Traditional inference methods for geostatistical modelling are notoriously computationally intensive, motivating the development of newer, approximate methods for geostatistical analysis or, more broadly, computational modelling of spatial processes. The appeal of faster methods is particularly great as the size of the region and number of spatial locations being modelled increases. METHODS: This work presents an applied comparison of four proposed 'fast' computational methods for spatial modelling and the software provided to implement them-Integrated Nested Laplace Approximation (INLA), tree boosting with Gaussian processes and mixed effect models (GPBoost), Fixed Rank Kriging (FRK) and Spatial Random Forests (SpRF). The four methods are illustrated by estimating malaria prevalence on two different spatial scales-country and continent. The performance of the four methods is compared on these data in terms of accuracy, computation time, and ease of implementation. RESULTS: Two of these methods-SpRF and GPBoost-do not scale well as the data size increases, and so are likely to be infeasible for larger-scale analysis problems. The two remaining methods-INLA and FRK-do scale well computationally, however the resulting model fits are very sensitive to the user's modelling assumptions and parameter choices. The binomial observation distribution commonly used for disease prevalence mapping with INLA fails to account for small-scale overdispersion present in the malaria prevalence data, which can lead to poor predictions. Selection of an appropriate alternative such as the Beta-binomial distribution is required to produce a reliable model fit. The small-scale random effect term in FRK overcomes this pitfall, but FRK model estimates are very reliant on providing a sufficient number and appropriate configuration of basis functions. Unfortunately the computation time for FRK increases rapidly with increasing basis resolution. CONCLUSIONS: INLA and FRK both enable scalable geostatistical modelling of malaria prevalence data. However care must be taken when using both methods to assess the fit of the model to data and plausibility of predictions, in order to select appropriate model assumptions and parameters.

Modelling temperature-driven changes in species associations across freshwater communities.

Due to global climate change-induced shifts in species distributions, estimating changes in community composition through the use of Species Distribution Models has become a key management tool. Being able to determine how species associations change along environmental gradients is likely to be pivotal in exploring the magnitude of future changes in species' distributions. This is particularly important in connectivity-limited ecosystems, such as freshwater ecosystems, where increased human translocation is creating species associations over previously unseen environmental gradients. Here, we use a large-scale presence-absence dataset of freshwater fish from lakes across the Fennoscandian region in a Joint Species Distribution Model, to measure the effect of temperature on species associations. We identified a trend of negative associations between species tolerant of cold waters and those tolerant of warmer waters, as well as positive associations between several more warm-tolerant species, with these associations often shifting depending on local temperatures. Our results confirm that freshwater ecosystems can expect to see a large-scale shift towards communities dominated by more warm-tolerant species. While there remains much work to be done to predict exactly where and when local extinctions may take place, the model implemented provides a starting-point for the exploration of climate-driven community trends. This approach is especially informative in regards to determining which species associations are most central in shaping future community composition, and which areas are most vulnerable to local extinctions.

Reconstructing the early global dynamics of under-ascertained COVID-19 cases and infections.

BACKGROUND: Asymptomatic or subclinical SARS-CoV-2 infections are often unreported, which means that confirmed case counts may not accurately reflect underlying epidemic dynamics. Understanding the level of ascertainment (the ratio of confirmed symptomatic cases to the true number of symptomatic individuals) and undetected epidemic progression is crucial to informing COVID-19 response planning, including the introduction and relaxation of control measures. Estimating case ascertainment over time allows for accurate estimates of specific outcomes such as seroprevalence, which is essential for planning control measures. METHODS: Using reported data on COVID-19 cases and fatalities globally, we estimated the proportion of symptomatic cases (i.e. any person with any of fever ≥ 37.5 °C, cough, shortness of breath, sudden onset of anosmia, ageusia or dysgeusia illness) that were reported in 210 countries and territories, given those countries had experienced more than ten deaths. We used published estimates of the baseline case fatality ratio (CFR), which was adjusted for delays and under-ascertainment, then calculated the ratio of this baseline CFR to an estimated local delay-adjusted CFR to estimate the level of under-ascertainment in a particular location. We then fit a Bayesian Gaussian process model to estimate the temporal pattern of under-ascertainment. RESULTS: Based on reported cases and deaths, we estimated that, during March 2020, the median percentage of symptomatic cases detected across the 84 countries which experienced more than ten deaths ranged from 2.4% (Bangladesh) to 100% (Chile). Across the ten countries with the highest number of total confirmed cases as of 6 July 2020, we estimated that the peak number of symptomatic cases ranged from 1.4 times (Chile) to 18 times (France) larger than reported. Comparing our model with national and regional seroprevalence data where available, we find that our estimates are consistent with observed values. Finally, we estimated seroprevalence for each country. As of 7 June, our seroprevalence estimates range from 0% (many countries) to 13% (95% CrI 5.6-24%) (Belgium). CONCLUSIONS: We found substantial under-ascertainment of symptomatic cases, particularly at the peak of the first wave of the SARS-CoV-2 pandemic, in many countries. Reported case counts will therefore likely underestimate the rate of outbreak growth initially and underestimate the decline in the later stages of an epidemic. Although there was considerable under-reporting in many locations, our estimates were consistent with emerging serological data, suggesting that the proportion of each country's population infected with SARS-CoV-2 worldwide is generally low.

Mapping under-5 and neonatal mortality in Africa, 2000-15: a baseline analysis for the Sustainable Development Goals.

BACKGROUND: During the Millennium Development Goal (MDG) era, many countries in Africa achieved marked reductions in under-5 and neonatal mortality. Yet the pace of progress toward these goals substantially varied at the national level, demonstrating an essential need for tracking even more local trends in child mortality. With the adoption of the Sustainable Development Goals (SDGs) in 2015, which established ambitious targets for improving child survival by 2030, optimal intervention planning and targeting will require understanding of trends and rates of progress at a higher spatial resolution. In this study, we aimed to generate high-resolution estimates of under-5 and neonatal all-cause mortality across 46 countries in Africa. METHODS: We assembled 235 geographically resolved household survey and census data sources on child deaths to produce estimates of under-5 and neonatal mortality at a resolution of 5 × 5 km grid cells across 46 African countries for 2000, 2005, 2010, and 2015. We used a Bayesian geostatistical analytical framework to generate these estimates, and implemented predictive validity tests. In addition to reporting 5 × 5 km estimates, we also aggregated results obtained from these estimates into three different levels-national, and subnational administrative levels 1 and 2-to provide the full range of geospatial resolution that local, national, and global decision makers might require. FINDINGS: Amid improving child survival in Africa, there was substantial heterogeneity in absolute levels of under-5 and neonatal mortality in 2015, as well as the annualised rates of decline achieved from 2000 to 2015. Subnational areas in countries such as Botswana, Rwanda, and Ethiopia recorded some of the largest decreases in child mortality rates since 2000, positioning them well to achieve SDG targets by 2030 or earlier. Yet these places were the exception for Africa, since many areas, particularly in central and western Africa, must reduce under-5 mortality rates by at least 8·8% per year, between 2015 and 2030, to achieve the SDG 3.2 target for under-5 mortality by 2030. INTERPRETATION: In the absence of unprecedented political commitment, financial support, and medical advances, the viability of SDG 3.2 achievement in Africa is precarious at best. By producing under-5 and neonatal mortality rates at multiple levels of geospatial resolution over time, this study provides key information for decision makers to target interventions at populations in the greatest need. In an era when precision public health increasingly has the potential to transform the design, implementation, and impact of health programmes, our 5 × 5 km estimates of child mortality in Africa provide a baseline against which local, national, and global stakeholders can map the pathways for ending preventable child deaths by 2030. FUNDING: Bill & Melinda Gates Foundation.

Local, national, and regional viral haemorrhagic fever pandemic potential in Africa: a multistage analysis.

BACKGROUND: Predicting when and where pathogens will emerge is difficult, yet, as shown by the recent Ebola and Zika epidemics, effective and timely responses are key. It is therefore crucial to transition from reactive to proactive responses for these pathogens. To better identify priorities for outbreak mitigation and prevention, we developed a cohesive framework combining disparate methods and data sources, and assessed subnational pandemic potential for four viral haemorrhagic fevers in Africa, Crimean-Congo haemorrhagic fever, Ebola virus disease, Lassa fever, and Marburg virus disease. METHODS: In this multistage analysis, we quantified three stages underlying the potential of widespread viral haemorrhagic fever epidemics. Environmental suitability maps were used to define stage 1, index-case potential, which assesses populations at risk of infection due to spillover from zoonotic hosts or vectors, identifying where index cases could present. Stage 2, outbreak potential, iterates upon an existing framework, the Index for Risk Management, to measure potential for secondary spread in people within specific communities. For stage 3, epidemic potential, we combined local and international scale connectivity assessments with stage 2 to evaluate possible spread of local outbreaks nationally, regionally, and internationally. FINDINGS: We found epidemic potential to vary within Africa, with regions where viral haemorrhagic fever outbreaks have previously occurred (eg, western Africa) and areas currently considered non-endemic (eg, Cameroon and Ethiopia) both ranking highly. Tracking transitions between stages showed how an index case can escalate into a widespread epidemic in the absence of intervention (eg, Nigeria and Guinea). Our analysis showed Chad, Somalia, and South Sudan to be highly susceptible to any outbreak at subnational levels. INTERPRETATION: Our analysis provides a unified assessment of potential epidemic trajectories, with the aim of allowing national and international agencies to pre-emptively evaluate needs and target resources. Within each country, our framework identifies at-risk subnational locations in which to improve surveillance, diagnostic capabilities, and health systems in parallel with the design of policies for optimal responses at each stage. In conjunction with pandemic preparedness activities, assessments such as ours can identify regions where needs and provisions do not align, and thus should be targeted for future strengthening and support. FUNDING: Paul G Allen Family Foundation, Bill & Melinda Gates Foundation, Wellcome Trust, UK Department for International Development.

Modelling the relative abundance of the primary African vectors of malaria before and after the implementation of indoor, insecticide-based vector control.

BACKGROUND: Malaria remains a heavy burden across sub-Saharan Africa where transmission is maintained by some of the world's most efficient vectors. Indoor insecticide-based control measures have significantly reduced transmission, yet elimination remains a distant target. Knowing the relative abundance of the primary vector species can provide transmission models with much needed information to guide targeted control measures. Moreover, understanding how existing interventions are impacting on these relative abundances highlights where alternative control (e.g., larval source management) is needed. METHODS: Using the habitat suitability probabilities generated by predictive species distribution models combined with data collated from the literature, a multinomial generalized additive model was applied to produce relative abundance estimates for Anopheles arabiensis, Anopheles funestus and Anopheles gambiae/Anopheles coluzzii. Using pre- and post-intervention abundance data, estimates of the effect of indoor insecticide-based interventions on these relative abundances were made and are illustrated in post-intervention maps. RESULTS: Conditional effect plots and relative abundance maps illustrate the individual species' predicted habitat suitability and how they interact when in sympatry. Anopheles arabiensis and An. funestus show an affinity in habitat preference at the expense of An. gambiae/An. coluzzii, whereas increasing habitat suitability for An. gambiae/An. coluzzii is conversely less suitable for An. arabiensis but has little effect on An. funestus. Indoor insecticide-based interventions had a negative impact on the relative abundance of An. funestus, and a lesser effect on An. arabiensis. Indoor residual spraying had the greatest impact on the relative abundance of An. funestus, and a lesser effect on An. gambiae/An. coluzzii. Insecticide-treated bed nets reduced the relative abundance of both species equally. These results do not indicate changes in the absolute abundance of these species, which may be reduced for all species overall. CONCLUSIONS: The maps presented here highlight the interactions between the primary vector species in sub-Saharan Africa and demonstrate that An. funestus is more susceptible to certain indoor-based insecticide interventions than An. gambiae/An. coluzzii, which in turn, is more susceptible than An. arabiensis. This may provide An. arabiensis with a competitive advantage where it is found in sympatry with other more endophilic vectors, and potentially increase the need for outdoor-based vector interventions to deal with any residual transmission barring the way to malaria elimination.

Integrating vector control across diseases.

BACKGROUND: Vector-borne diseases cause a significant proportion of the overall burden of disease across the globe, accounting for over 10 % of the burden of infectious diseases. Despite the availability of effective interventions for many of these diseases, a lack of resources prevents their effective control. Many existing vector control interventions are known to be effective against multiple diseases, so combining vector control programmes to simultaneously tackle several diseases could offer more cost-effective and therefore sustainable disease reductions. DISCUSSION: The highly successful cross-disease integration of vaccine and mass drug administration programmes in low-resource settings acts a precedent for cross-disease vector control. Whilst deliberate implementation of vector control programmes across multiple diseases has yet to be trialled on a large scale, a number of examples of 'accidental' cross-disease vector control suggest the potential of such an approach. Combining contemporary high-resolution global maps of the major vector-borne pathogens enables us to quantify overlap in their distributions and to estimate the populations jointly at risk of multiple diseases. Such an analysis shows that over 80 % of the global population live in regions of the world at risk from one vector-borne disease, and more than half the world's population live in areas where at least two different vector-borne diseases pose a threat to health. Combining information on co-endemicity with an assessment of the overlap of vector control methods effective against these diseases allows us to highlight opportunities for such integration. Malaria, leishmaniasis, lymphatic filariasis, and dengue are prime candidates for combined vector control. All four of these diseases overlap considerably in their distributions and there is a growing body of evidence for the effectiveness of insecticide-treated nets, screens, and curtains for controlling all of their vectors. The real-world effectiveness of cross-disease vector control programmes can only be evaluated by large-scale trials, but there is clear evidence of the potential of such an approach to enable greater overall health benefit using the limited funds available.

Emergence and potential for spread of Chikungunya virus in Brazil.

BACKGROUND: In December 2013, an outbreak of Chikungunya virus (CHIKV) caused by the Asian genotype was notified in the Caribbean. The outbreak has since spread to 38 regions in the Americas. By September 2014, the first autochthonous CHIKV infections were confirmed in Oiapoque, North Brazil, and in Feira de Santana, Northeast Brazil. METHODS: We compiled epidemiological and clinical data on suspected CHIKV cases in Brazil and polymerase-chain-reaction-based diagnostic was conducted on 68 serum samples from patients with symptom onset between April and September 2014. Two imported and four autochthonous cases were selected for virus propagation, RNA isolation, full-length genome sequencing, and phylogenetic analysis. We then followed CDC/PAHO guidelines to estimate the risk of establishment of CHIKV in Brazilian municipalities. RESULTS: We detected 41 CHIKV importations and 27 autochthonous cases in Brazil. Epidemiological and phylogenetic analyses indicated local transmission of the Asian CHIKV genotype in Oiapoque. Unexpectedly, we also discovered that the ECSA genotype is circulating in Feira de Santana. The presumed index case of the ECSA genotype was an individual who had recently returned from Angola and developed symptoms in Feira de Santana. We estimate that, if CHIKV becomes established in Brazil, transmission could occur in 94% of municipalities in the country and provide maps of the risk of importation of each strain of CHIKV in Brazil. CONCLUSIONS: The etiological strains associated with the early-phase CHIKV outbreaks in Brazil belong to the Asian and ECSA genotypes. Continued surveillance and vector mitigation strategies are needed to reduce the future public health impact of CHIKV in the Americas.

Defining the relationship between Plasmodium vivax parasite rate and clinical disease.

BACKGROUND: Though essential to the development and evaluation of national malaria control programmes, precise enumeration of the clinical illness burden of malaria in endemic countries remains challenging where local surveillance systems are incomplete. Strategies to infer annual incidence rates from parasite prevalence survey compilations have proven effective in the specific case of Plasmodium falciparum, but have yet to be developed for Plasmodium vivax. Moreover, defining the relationship between P. vivax prevalence and clinical incidence may also allow levels of endemicity to be inferred for areas where the information balance is reversed, that is, incident case numbers are more widely gathered than parasite surveys; both applications ultimately facilitating cartographic estimates of P. vivax transmission intensity and its ensuring disease burden. METHODS: A search for active case detection surveys was conducted and the recorded incidence values were matched to local, contemporary parasite rate measures and classified to geographic zones of differing relapse phenotypes. A hierarchical Bayesian model was fitted to these data to quantify the relationship between prevalence and incidence while accounting for variation among relapse zones. RESULTS: The model, fitted with 176 concurrently measured P. vivax incidence and prevalence records, was a linear regression of the logarithm of incidence against the logarithm of age-standardized prevalence. Specific relationships for the six relapse zones where data were available were drawn, as well as a pooled overall relationship. The slope of the curves varied among relapse zones; zones with short predicted time to relapse had steeper slopes than those observed to contain long-latency relapse phenotypes. CONCLUSIONS: The fitted relationships, along with appropriate uncertainty metrics, allow for estimates of clinical incidence of known confidence to be made from wherever P. vivax prevalence data are available. This is a prerequisite for cartographic-based inferences about the global burden of morbidity due to P. vivax, which will be used to inform control efforts.

Geographical variation in Plasmodium vivax relapse.

BACKGROUND: Plasmodium vivax has the widest geographic distribution of the human malaria parasites and nearly 2.5 billion people live at risk of infection. The control of P. vivax in individuals and populations is complicated by its ability to relapse weeks to months after initial infection. Strains of P. vivax from different geographical areas are thought to exhibit varied relapse timings. In tropical regions strains relapse quickly (three to six weeks), whereas those in temperate regions do so more slowly (six to twelve months), but no comprehensive assessment of evidence has been conducted. Here observed patterns of relapse periodicity are used to generate predictions of relapse incidence within geographic regions representative of varying parasite transmission. METHODS: A global review of reports of P. vivax relapse in patients not treated with a radical cure was conducted. Records of time to first P. vivax relapse were positioned by geographic origin relative to expert opinion regions of relapse behaviour and epidemiological zones. Mixed-effects meta-analysis was conducted to determine which geographic classification best described the data, such that a description of the pattern of relapse periodicity within each region could be described. Model outputs of incidence and mean time to relapse were mapped to illustrate the global variation in relapse. RESULTS: Differences in relapse periodicity were best described by a historical geographic classification system used to describe malaria transmission zones based on areas sharing zoological and ecological features. Maps of incidence and time to relapse showed high relapse frequency to be predominant in tropical regions and prolonged relapse in temperate areas. CONCLUSIONS: The results indicate that relapse periodicity varies systematically by geographic region and are categorized by nine global regions characterized by similar malaria transmission dynamics. This indicates that relapse may be an adaptation evolved to exploit seasonal changes in vector survival and therefore optimize transmission. Geographic patterns in P. vivax relapse are important to clinicians treating individual infections, epidemiologists trying to infer P. vivax burden, and public health officials trying to control and eliminate the disease in human populations.

Estimating measures to reduce the transmission of SARS-CoV-2 in Australia to guide a 'National Plan' to reopening.

The availability of COVID-19 vaccines promised a reduction in the severity of disease and relief from the strict public health and social measures (PHSMs) imposed in many countries to limit spread and burden of COVID-19. We were asked to define vaccine coverage thresholds for Australia's transition to easing restrictions and reopening international borders. Using evidence of vaccine effectiveness against the then-circulating Delta variant, we used a mathematical model to determine coverage targets. The absence of any COVID-19 infections in many sub-national jurisdictions in Australia posed particular methodological challenges. We used a novel metric called Transmission Potential (TP) as a proxy measure of the population-level effective reproduction number. We estimated TP of the Delta variant under a range of PHSMs, test-trace-isolate-quarantine (TTIQ) efficiencies, vaccination coverage thresholds, and age-based vaccine allocation strategies. We found that high coverage across all ages (≥70%) combined with ongoing TTIQ and minimal PHSMs was sufficient to avoid lockdowns. At lesser coverage (≤60%) rapid case escalation risked overwhelming of the health sector or the need to reimpose stricter restrictions. Maintaining low case numbers was most beneficial for health and the economy, and at higher coverage levels (≥80%) further easing of restrictions was deemed possible. These results directly informed easing of COVID-19 restrictions in Australia.

Vegetation structure drives mosquito community composition in UK's largest managed lowland wetland.

PURPOSE: The rising burden of mosquito-borne diseases in Europe extends beyond urban areas, encompassing rural and semi-urban regions near managed and natural wetlands evidenced by recent outbreaks of Usutu and West Nile viruses. While wetland management policies focus on biodiversity and ecosystem services, few studies explore the impact on mosquito vectors. METHODS: Our research addresses this gap, examining juvenile mosquito and aquatic predator communities in 67 ditch sites within a South England coastal marsh subjected to different wetland management tiers. Using joint distribution models, we analyse how mosquito communities respond to abiotic and biotic factors influenced by wetland management. RESULTS: Of the 12 mosquito species identified, Culiseta annulata (Usutu virus vector) and Culex pipiens (Usutu and West Nile virus vector) constitute 47% of 6825 larval mosquitoes. Abundant predators include Coleoptera (water beetles) adults, Corixidae (water boatmen) and Zygoptera (Damselfy) larvae. Models reveal that tier 3 management sites (higher winter water levels, lower agricultural intensity) associated with shade and less floating vegetation are preferred by specific mosquito species. All mosquito species except Anopheles maculipennis s.l., are negatively impacted by potential predators. Culiseta annulata shows positive associations with shaded and turbid water, contrary to preferences of Corixidae predators. CONCLUSIONS: Tier 3 areas managed for biodiversity, characterised by higher seasonal water levels and reduced livestock grazing intensity, provide favourable habitats for key mosquito species that are known vectors of arboviruses, such as Usutu and West Nile. Our findings emphasise the impact of biodiversity-focused wetland management, altering mosquito breeding site vegetation to enhance vector suitability. Further exploration of these trade-offs is crucial for comprehending the broader implications of wetland management.

Estimating the impact of test-trace-isolate-quarantine systems on SARS-CoV-2 transmission in Australia.

BACKGROUND: Australian states and territories used test-trace-isolate-quarantine (TTIQ) systems extensively in their response to the COVID-19 pandemic in 2020-2021. We report on an analysis of Australian case data to estimate the impact of test-trace-isolate-quarantine systems on SARS-CoV-2 transmission. METHODS: Our analysis uses a novel mathematical modelling framework and detailed surveillance data on COVID-19 cases including dates of infection and dates of isolation. First, we directly translate an empirical distribution of times from infection to isolation into reductions in potential for onward transmission during periods of relatively low caseloads (tens to hundreds of reported cases per day). We then apply a simulation approach, validated against case data, to assess the impact of case-initiated contact tracing on transmission during a period of relatively higher caseloads and system stress (up to thousands of cases per day). RESULTS: We estimate that under relatively low caseloads in the state of New South Wales (tens of cases per day), TTIQ contributed to a 54% reduction in transmission. Under higher caseloads in the state of Victoria (hundreds of cases per day), TTIQ contributed to a 42% reduction in transmission. Our results also suggest that case-initiated contact tracing can support timely quarantine in times of system stress (thousands of cases per day). CONCLUSION: Contact tracing systems for COVID-19 in Australia were highly effective and adaptable in supporting the national suppression strategy from 2020-21, prior to the emergence of the Omicron variant in November 2021. TTIQ systems were critical to the maintenance of the strong suppression strategy and were more effective when caseloads were (relatively) low.

The global distribution and the risk prediction of relapsing fever group Borrelia: a data review with modelling analysis.

BACKGROUND: The recent discovery of emerging relapsing fever group Borrelia (RFGB) species, such as Borrelia miyamotoi, poses a growing threat to public health. However, the global distribution and associated risk burden of these species remain uncertain. We aimed to map the diversity, distribution, and potential infection risk of RFGB. METHODS: We searched PubMed, Web of Science, GenBank, CNKI, and eLibrary from Jan 1, 1874, to Dec 31, 2022, for published articles without language restriction to extract distribution data for RFGB detection in vectors, animals, and humans, and clinical information about human patients. Only articles documenting RFGB infection events were included in this study, and data for RFGB detection in vectors, animals, or humans were composed into a dataset. We used three machine learning algorithms (boosted regression trees, random forest, and least absolute shrinkage and selection operator logistic regression) to assess the environmental, ecoclimatic, biological, and socioeconomic factors associated with the occurrence of four major RFGB species: Borrelia miyamotoi, Borrelia lonestari, Borrelia crocidurae, and Borrelia hermsii; and mapped their worldwide risk level. FINDINGS: We retrieved 13 959 unique studies, among which 697 met the selection criteria and were used for data extraction. 29 RFGB species have been recorded worldwide, of which 27 have been identified from 63 tick species, 12 from 61 wild animals, and ten from domestic animals. 16 RFGB species caused human infection, with a cumulative count of 26 583 cases reported from Jan 1, 1874, to Dec 31, 2022. Borrelia recurrentis (17 084 cases) and Borrelia persica (2045 cases) accounted for the highest proportion of human infection. B miyamotoi showed the widest distribution among all RFGB, with a predicted environmentally suitable area of 6·92 million km2, followed by B lonestari (1·69 million km2), B crocidurae (1·67 million km2), and B hermsii (1·48 million km2). The habitat suitability index of vector ticks and climatic factors, such as the annual mean temperature, have the most significant effect among all predictive models for the geographical distribution of the four major RFGB species. INTERPRETATION: The predicted high-risk regions are considerably larger than in previous reports. Identification, surveillance, and diagnosis of RFGB infections should be prioritised in high-risk areas, especially within low-income regions. FUNDING: National Key Research and Development Program of China.

Mapping the distribution of Nipah virus infections: a geospatial modelling analysis.

BACKGROUND: Nipah virus is a zoonotic paramyxovirus responsible for disease outbreaks with high fatality rates in south and southeast Asia. However, knowledge of the potential geographical extent and risk patterns of the virus is poor. We aimed to establish an integrated spatiotemporal and phylogenetic database of Nipah virus infections in humans and animals across south and southeast Asia. METHODS: In this geospatial modelling analysis, we developed an integrated database containing information on the distribution of Nipah virus infections in humans and animals from 1998 to 2021. We conducted phylodynamic analysis to examine the evolution and migration pathways of the virus and meta-analyses to estimate the adjusted case-fatality rate. We used two boosted regression tree models to identify the potential ecological drivers of Nipah virus occurrences in spillover events and endemic areas, and mapped potential risk areas for Nipah virus endemicity. FINDINGS: 749 people and eight bat species across nine countries were documented as being infected with Nipah virus. On the basis of 66 complete genomes of the virus, we identified two clades-the Bangladesh clade and the Malaysia clade-with the time of the most recent common ancestor estimated to be 1863. Adjusted case-fatality rates varied widely between countries and were higher for the Bangladesh clade than for the Malaysia clade. Multivariable meta-regression analysis revealed significant relationships between case-fatality rate estimates and viral clade (p=0·0021), source country (p=0·016), proportion of male patients (p=0·036), and travel time to health-care facilities (p=0·036). Temperature-related bioclimate variables and the probability of occurrence of Pteropus medius were important contributors to both the spillover and the endemic infection models. INTERPRETATION: The suitable niches for Nipah virus are more extensive than previously reported. Future surveillance efforts should focus on high-risk areas informed by updated projections. Specifically, intensifying zoonotic surveillance efforts, enhancing laboratory testing capacity, and implementing public health education in projected high-risk areas where no human cases have been reported to date will be crucial. Additionally, strengthening wildlife surveillance and investigating potential modes of transmission in regions with documented human cases is needed. FUNDING: The Key Research and Development Program of China.

Introduction of Aedes aegypti mosquitoes carrying wAlbB Wolbachia sharply decreases dengue incidence in disease hotspots.

Partial replacement of resident Aedes aegypti mosquitoes with introduced mosquitoes carrying certain strains of inherited Wolbachia symbionts can result in transmission blocking of dengue and other viruses of public health importance. Wolbachia strain wAlbB is an effective transmission blocker and stable at high temperatures, making it particularly suitable for hot tropical climates. Following trial field releases in Malaysia, releases using wAlbB Ae. aegypti have become operationalized by the Malaysian health authorities. We report here on an average reduction in dengue fever of 62.4% (confidence intervals 50-71%) in 20 releases sites when compared to 76 control sites in high-rise residential areas. Importantly the level of dengue reduction increased with Wolbachia frequency, with 75.8% reduction (61-87%) estimated at 100% Wolbachia frequency. These findings indicate large impacts of wAlbB Wolbachia invasions on dengue fever incidence in an operational setting, with incidence expected to further decrease as wider areas are invaded.

A modelling approach to estimate the transmissibility of SARS-CoV-2 during periods of high, low, and zero case incidence.

Against a backdrop of widespread global transmission, a number of countries have successfully brought large outbreaks of COVID-19 under control and maintained near-elimination status. A key element of epidemic response is the tracking of disease transmissibility in near real-time. During major outbreaks, the effective reproduction number can be estimated from a time-series of case, hospitalisation or death counts. In low or zero incidence settings, knowing the potential for the virus to spread is a response priority. Absence of case data means that this potential cannot be estimated directly. We present a semi-mechanistic modelling framework that draws on time-series of both behavioural data and case data (when disease activity is present) to estimate the transmissibility of SARS-CoV-2 from periods of high to low - or zero - case incidence, with a coherent transition in interpretation across the changing epidemiological situations. Of note, during periods of epidemic activity, our analysis recovers the effective reproduction number, while during periods of low - or zero - case incidence, it provides an estimate of transmission risk. This enables tracking and planning of progress towards the control of large outbreaks, maintenance of virus suppression, and monitoring the risk posed by re-introduction of the virus. We demonstrate the value of our methods by reporting on their use throughout 2020 in Australia, where they have become a central component of the national COVID-19 response.

Forecasting COVID-19 activity in Australia to support pandemic response: May to October 2020.

As of January 2021, Australia had effectively controlled local transmission of COVID-19 despite a steady influx of imported cases and several local, but contained, outbreaks in 2020. Throughout 2020, state and territory public health responses were informed by weekly situational reports that included an ensemble forecast of daily COVID-19 cases for each jurisdiction. We present here an analysis of one forecasting model included in this ensemble across the variety of scenarios experienced by each jurisdiction from May to October 2020. We examine how successfully the forecasts characterised future case incidence, subject to variations in data timeliness and completeness, showcase how we adapted these forecasts to support decisions of public health priority in rapidly-evolving situations, evaluate the impact of key model features on forecast skill, and demonstrate how to assess forecast skill in real-time before the ground truth is known. Conditioning the model on the most recent, but incomplete, data improved the forecast skill, emphasising the importance of developing strong quantitative models of surveillance system characteristics, such as ascertainment delay distributions. Forecast skill was highest when there were at least 10 reported cases per day, the circumstances in which authorities were most in need of forecasts to aid in planning and response.