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BackgroundAedes (Stegomyia)-borne diseases are an expanding global threat, but gaps in surveillance make comprehensive and comparable risk assessments challenging. Geostatistical models combine data from multiple locations and use links with environmental and socioeconomic factors to make predictive risk maps. Here we systematically review past approaches to map risk for differentAedes-borne arboviruses from local to global scales, identifying differences and similarities in the data types, covariates, and modelling approaches used.MethodsWe searched on-line databases for predictive risk mapping studies for dengue, Zika, chikungunya, and yellow fever with no geographical or date restrictions. We included studies that needed to parameterise or fit their model to real-world epidemiological data and make predictions to new spatial locations of some measure of population-level risk of viral transmission (e.g. incidence, occurrence, suitability, etc).ResultsWe found a growing number of arbovirus risk mapping studies across all endemic regions and arboviral diseases, with a total of 183 papers published 2002-2022 with the largest increases shortly following major epidemics. Three dominant use cases emerged: i) global maps to identify limits of transmission, estimate burden and assess impacts of future global change, ii) regional models used to predict the spread of major epidemics between countries and iii) national and sub-national models that use local datasets to better understand transmission dynamics to improve outbreak detection and response. Temperature and rainfall were the most popular choice of covariates (included in 50% and 40% of studies respectively) but variables such as human mobility are increasingly being included. Surprisingly, few studies (22%, 33/148) robustly tested combinations of covariates from different domains (e.g. climatic, sociodemographic, ecological, etc) and only 48% of studies assessed predictive performance via out-of-sample validation procedures.ConclusionsHere we show that approaches to map risk for different arboviruses have diversified in response to changing use cases, epidemiology and data availability. We outline specific recommendations for future studies regarding aims and data choice, covariate selection, model formulation and evaluation.Author SummaryAedes-borne arboviruses such as dengue, Zika, chikungunya, and yellow fever pose a growing global threat. It is crucial to map their risk to target interventions and control their spread. A review of 183 studies found that risk mapping methods have evolved over time to respond to changing epidemiology and data availability. Initially, mapping risk involved using data from multiple areas and satellite imagery to develop models predicting transmission risk on a global or continental scale. Following Zika and chikungunya epidemics, mechanistic models based on national-level incidence data have been utilised to track the spread of epidemics across countries. The use of case-based surveillance systems has enabled more precise and detailed predictions at sub-national levels. Of the studies reviewed, half included temperature and rainfall as covariates, and human mobility was increasingly accounted for in arbovirus risk mapping. However, only 33 of the 148 studies robustly selected the variables included in their predictions, and only half of the studies assessed their accuracy against new data. The review suggests that future risk mapping studies should consider the purpose of the map, data quality, and methodological innovations to improve accuracy of risk maps to ensure they are useful for informing control ofAedes-borne arboviruses.

Dengue virus (DENV) causes repeated outbreaks of disease in endemic areas, with patterns of local transmission strongly influenced by seasonality, importation via human movement, immunity, and vector control efforts. An understanding of how each of these interacts to enable endemic transmission (continual circulation of local virus strains) is largely unknown. There are times of the year when no cases are reported, often for extended periods of time, perhaps wrongly implying the successful eradication of a local strain from that area. Individuals who presented at a clinic or hospital in four communes in Nha Trang, Vietnam, were initially tested for DENV antigen presence. Enrolled positive individuals then had their corresponding household members invited to participate, and those who enrolled were tested for DENV. The presence of viral nucleic acid in all samples was confirmed using quantitative polymerase chain reaction, and positive samples were then whole-genome sequenced using an amplicon and target enrichment library preparation techniques and Illumina MiSeq sequencing technology. Generated consensus genome sequences were then analysed using phylogenetic tree reconstruction to categorise sequences into clades with a common ancestor, enabling investigations of both viral clade persistence and introductions. Hypothetical introduction dates were additionally assessed using a molecular clock model that calculated the time to the most recent common ancestor (TMRCA). We obtained 511 DENV whole-genome sequences covering four serotypes and more than ten distinct viral clades. For five of these clades, we had sufficient data to show that the same viral lineage persisted for at least several months. We noted that some clades persisted longer than others during the sampling time, and by comparison with other published sequences from elsewhere in Vietnam and around the world, we saw that at least two different viral lineages were introduced into the population during the study period (April 2017–2019). Next, by inferring the TMRCA from the construction of molecular clock phylogenies, we predicted that two of the viral lineages had been present in the study population for over a decade. We observed five viral lineages co-circulating in Nha Trang from three DENV serotypes, with two likely to have remained as uninterrupted transmission chains for a decade. This suggests clade cryptic persistence in the area, even during periods of low reported incidence.

Despite multi-modal therapies for patients with malignant brain tumors, their median survival is ex vivo activated haploidentical NK cells in six patients with recurrent glioblastoma multiform (GBM) and malignant brain tumors resistance to chemo/radio therapy. The results showed that local administration of the haploidentical NK cells in malignant brain tumors is safe, feasible, tolerated at higher dose and also is cost effective.

ObjectivesChad reports the second highest maternal mortality worldwide. We conducted a survey in Sila region in southeast Chad to estimate the use of maternal health services (MHS) and to identify barriers to access MHS.DesignRetrospective cross-sectional, population-based survey using two-stage cluster sampling methodology. The survey consisted of two strata, Koukou Angarana and Goz Beida district in Sila region. We conducted systematic random sampling proportional to population size to select settlements in each strata in the first sampling stage; and in the second stage we selected households in the settlements using random walk procedure. We calculated survey-design-weighted proportions with 95% CIs. We performed univariate analysis and multivariable logistic regression to identify impact factors associated with the use of MHS.SettingWe interviewed women in selected households in Sila region in 2019.ParticipantsWomen at reproductive age, who have given birth in the previous 2 years and are living in Koukou Angarana and Goz Beida district.Primary outcomesUse of and access barriers to MHS including antenatal care (ANC), delivery care in a health facility (DC), postnatal care (PNC) and contraceptive methods.ResultsIn total, 624 women participated. Median age was 28 years, 95.4% were illiterate and 95.7% married. Use of ANC, DC and PNC was reported by 57.6% (95% CI: 49.3% to 65.5%), 22.5% (95% CI: 15.7% to 31.1%) and 32.9% (95% CI: 25.8% to 40.9%), respectively. Use of MHS was lower in rural compared with urban settings. Having attended ANC increased the odds of using DC by 4.3 (1.5–12.2) and using PNC by 6.4 (3.7–11.1). Factors related to transport and to culture and belief were the most frequently stated access barriers to MHS.ConclusionIn Sila region, use of MHS is low and does not meet WHO-defined standards regarding maternal health. Among all services, use of ANC was better than for other MHS. ANC usage is positively associated with the use of further life-saving MHS including DC and could be used as an entry point to the community. To increase use of MHS, interventions should include infrastructural improvements as well as community-based approaches to overcome access barriers related to culture and belief.

Background SARS-CoV-2 is known to transmit in hospital settings, but the contribution of infections acquired in hospitals to the epidemic at a national scale is unknown. Methods We used comprehensive national English datasets to determine the number of COVID-19 patients with identified hospital-acquired infections (with symptom onset > 7 days after admission and before discharge) in acute English hospitals up to August 2020. As patients may leave the hospital prior to detection of infection or have rapid symptom onset, we combined measures of the length of stay and the incubation period distribution to estimate how many hospital-acquired infections may have been missed. We used simulations to estimate the total number (identified and unidentified) of symptomatic hospital-acquired infections, as well as infections due to onward community transmission from missed hospital-acquired infections, to 31st July 2020. Results In our dataset of hospitalised COVID-19 patients in acute English hospitals with a recorded symptom onset date (n = 65,028), 7% were classified as hospital-acquired. We estimated that only 30% (range across weeks and 200 simulations: 20–41%) of symptomatic hospital-acquired infections would be identified, with up to 15% (mean, 95% range over 200 simulations: 14.1–15.8%) of cases currently classified as community-acquired COVID-19 potentially linked to hospital transmission. We estimated that 26,600 (25,900 to 27,700) individuals acquired a symptomatic SARS-CoV-2 infection in an acute Trust in England before 31st July 2020, resulting in 15,900 (15,200–16,400) or 20.1% (19.2–20.7%) of all identified hospitalised COVID-19 cases. Conclusions Transmission of SARS-CoV-2 to hospitalised patients likely caused approximately a fifth of identified cases of hospitalised COVID-19 in the “first wave” in England, but less than 1% of all infections in England. Using time to symptom onset from admission for inpatients as a detection method likely misses a substantial proportion (> 60%) of hospital-acquired infections.

Hospital-based transmission played a dominant role in MERS-CoV and SARS-CoV epidemics but large-scale studies of its role in the SARS-CoV-2 pandemic are lacking. Such transmission risks spreading the virus to the most vulnerable individuals and can have wider-scale impacts through hospital-community interactions. Using data from acute hospitals in England we quantify within-hospital transmission, evaluate likely pathways of spread and factors associated with heightened transmission risk, and explore the wider dynamical consequences. We show that hospital transmission is likely to have been a major contributor to the burden of COVID-19 in England. We estimate that between June 2020 and March 2021 between 95,000 and 167,000 patients acquired SARS-CoV-2 in hospitals with nosocomially-infected patients likely to have been the main sources of transmission to other patients. Increased transmission to patients was associated with hospitals having fewer single rooms and lower heated volume per bed. Moreover, we show that reducing hospital transmission could substantially enhance the efficiency of punctuated lockdown measures in suppressing community transmission. These findings reveal the previously unrecognised scale of hospital transmission, have direct implications for targeting of hospital control measures, and highlight the need to design hospitals better-equipped to limit the transmission of future high consequence pathogens.

Summary Many infection prevention and control (IPC) interventions have been adopted by hospitals to limit nosocomial transmission of SARS-CoV-2. The aim of this systematic review is to identify evidence on the effectiveness of these interventions. We conducted a literature search of five databases (OVID MEDLINE, Embase, CENTRAL, COVID-19 Portfolio(pre-print), Web of Science). SWIFT ActiveScreener software was used to screen English titles and abstracts published between 1st January 2020 and 6th April 2021. Intervention studies, defined by Cochrane Effective Practice and Organisation of Care, that evaluated IPC interventions with an outcome of SARS-CoV-2 infection in either patients or healthcare workers were included. Personal protective equipment (PPE) was excluded as this intervention had been previously reviewed. Risks of bias were assessed using the Cochrane tool for randomised trials (RoB2) and non-randomized studies of interventions (ROBINS-I). From 23,156 screened articles, we identified seven articles that met the inclusion criteria, all of which evaluated interventions to prevent infections in healthcare workers and the majority of which were focused on effectiveness of prophylaxes. Due to heterogeneity in interventions, we did not conduct a meta-analysis. All agents used for prophylaxes have little to no evidence of effectiveness against SARS-CoV-2 infections. We did not find any studies evaluating the effectiveness of interventions including but not limited to screening, isolation and improved ventilation. There is limited evidence from interventional studies, excluding PPE, evaluating IPC measures for SARS-CoV-2. This review calls for urgent action to implement such studies to inform policies to protect our most vulnerable populations and healthcare workers.

BACKGROUND: The COVID-19 pandemic has resulted in unprecedented disruption to society, which indirectly affects infectious disease dynamics. We aimed to assess the effects of COVID-19-related disruption on dengue, a major expanding acute public health threat, in southeast Asia and Latin America.METHODS: We assembled data on monthly dengue incidence from WHO weekly reports, climatic data from ERA5, and population variables from WorldPop for 23 countries between January, 2014 and December, 2019 and fit a Bayesian regression model to explain and predict seasonal and multi-year dengue cycles. We compared model predictions with reported dengue data January to December, 2020, and assessed if deviations from projected incidence since March, 2020 are associated with specific public health and social measures (from the Oxford Coronavirus Government Response Tracer database) or human movement behaviours (as measured by Google mobility reports).FINDINGS: We found a consistent, prolonged decline in dengue incidence across many dengue-endemic regions that began in March, 2020 (2·28 million cases in 2020 vs 4·08 million cases in 2019; a 44·1% decrease). We found a strong association between COVID-19-related disruption (as measured independently by public health and social measures and human movement behaviours) and reduced dengue risk, even after taking into account other drivers of dengue cycles including climatic and host immunity (relative risk 0·01-0·17, pINTERPRETATION: In most countries, COVID-19-related disruption led to historically low dengue incidence in 2020. Continuous monitoring of dengue incidence as COVID-19-related restrictions are relaxed will be important and could give new insights into transmission processes and intervention options.FUNDING: National Key Research and Development Program of China and the Medical Research Council.

BackgroundSARS-CoV-2 spreads in hospitals, but the contribution of these settings to the overall COVID-19 burden at a national level is unknown.MethodsWe used comprehensive national English datasets and simulation modelling to determine the total burden (identified and unidentified) of symptomatic hospital-acquired infections. Those unidentified would either be 1) discharged before symptom onset (“missed”), or 2) have symptom onset 7 days or fewer from admission (“misclassified”). We estimated the contribution of “misclassified” cases and transmission from “missed” symptomatic infections to the English epidemic before 31st July 2020.FindingsIn our dataset of hospitalised COVID-19 patients in acute English Trusts with a recorded symptom onset date (n = 65,028), 7% were classified as hospital-acquired (with symptom onset 8 or more days after admission and before discharge). We estimated that only 30% (range across weeks and 200 simulations: 20-41%) of symptomatic hospital-acquired infections would be identified. Misclassified cases and onward transmission from missed infections could account for 15% (mean, 95% range over 200 simulations: 14·1%-15·8%) of cases currently classified as community-acquired COVID-19.From this, we estimated that 26,600 (25,900 to 27,700) individuals acquired a symptomatic SARS-CoV-2 infection in an acute Trust in England before 31st July 2020, resulting in 15,900 (15,200-16,400) or 20.1% (19.2%-20.7%) of all identified hospitalised COVID-19 cases.ConclusionsTransmission of SARS-CoV-2 to hospitalised patients likely caused approximately a fifth of identified cases of hospitalised COVID-19 in the “first wave”, but fewer than 1% of all SARS-CoV-2 infections in England. Using symptom onset as a detection method for hospital-acquired SARS-CoV-2 likely misses a substantial proportion (>60%) of hospital-acquired infections.FundingNational Institute for Health Research, UK Medical Research Council, Society for Laboratory Automation and Screening, UKRI, Wellcome Trust, Singapore National Medical Research Council.Research in contextEvidence before this studyWe searched PubMed with the terms “((national OR country) AND (contribution OR burden OR estimates) AND (“hospital-acquired” OR “hospital-associated” OR “nosocomial”)) AND Covid-19” for articles published in English up to July 1st 2021. This identified 42 studies, with no studies that had aimed to produce comprehensive national estimates of the contribution of hospital settings to the COVID-19 pandemic. Most studies focused on estimating seroprevalence or levels of infection in healthcare workers only, which were not our focus. Removing the initial national/country terms identified 120 studies, with no country level estimates. Several single hospital setting estimates exist for England and other countries, but the percentage of hospital-associated infections reported relies on identified cases in the absence of universal testing.Added value of this studyThis study provides the first national-level estimates of all symptomatic hospital-acquired infections with SARS-CoV-2 in England up to the 31st July 2020. Using comprehensive data, we calculate how many infections would be unidentified and hence can generate a total burden, impossible from just notification data. Moreover, our burden estimates for onward transmission suggest the contribution of hospitals to the overall infection burden.Implications of all the available evidenceLarge numbers of patients may become infected with SARS-CoV-2 in hospitals though only a small proportion of such infections are identified. Further work is needed to better understand how interventions can reduce such transmission and to better understand the contributions of hospital transmission to mortality.

Background Targeting interventions to areas that have recently experienced cases of disease is one strategy to contain outbreaks of infectious disease. Such case-area targeted interventions (CATI) have become an increasingly popular approach for dengue control but there is little evidence to suggest how precisely targeted or how recent cases need to be, to mount an effective response. The growing interest in the development of prophylactic and therapeutic drugs for dengue has also given new relevance for CATI strategies to interrupt transmission or deliver early treatment. Methods/Principal findings Here we develop a patch-based mathematical model of spatial dengue spread and fit it to spatiotemporal datasets from Singapore. Simulations from this model suggest CATI strategies could be effective, particularly if used in lower density areas. To maximise effectiveness, increasing the size of the radius around an index case should be prioritised even if it results in delays in the intervention being applied. This is partially because large intervention radii ensure individuals receive multiple and regular rounds of drug dosing or vector control, and thus boost overall coverage. Given equivalent efficacy, CATIs using prophylactic drugs are predicted to be more effective than adult mosquito-killing vector control methods and may even offer the possibility of interrupting individual chains of transmission if rapidly deployed. CATI strategies quickly lose their effectiveness if baseline transmission increases or case detection rates fall. Conclusions/Significance These results suggest CATI strategies can play an important role in dengue control but are likely to be most relevant for low transmission areas where high coverage of other non-reactive interventions already exists. Controlled field trials are needed to assess the field efficacy and practical constraints of large operational CATI strategies., Author summary In resource limited settings there is a pressing need for more efficient, more targeted ways of controlling transmission and preventing outbreaks. One option is to use case-area targeted interventions (CATI) that are focussed on areas that have recently reported disease cases. The effectiveness of such CATI strategies is highly dependent on how the disease spreads. Despite CATI strategies being widely used to control the vector-transmitted disease dengue, little evidence underpins its effectiveness. In this analysis we formulate a mathematical model designed to test the effectiveness of CATI strategies for dengue control in Singapore- a best case test scenario for the approach. Simulation from this model suggested CATI are likely to be effective for dengue, but need to have large (250m+) radii around index cases and may not be suitable in higher transmission areas. These results, when combined with limited field evidence of efficacy, suggest that CATI strategies are unlikely to be universally applicable dengue control tools. Only once high coverage with other (non-reactive) interventions has been achieved and comprehensive rapid disease surveillance has been established are CATI strategies likely to become efficient methods of disease control.

Background The COVID-19 pandemic has placed an unprecedented strain on health systems, with rapidly increasing demand for healthcare in hospitals and intensive care units (ICUs) worldwide. As the pandemic escalates, determining the resulting needs for healthcare resources (beds, staff, equipment) has become a key priority for many countries. Projecting future demand requires estimates of how long patients with COVID-19 need different levels of hospital care. Methods We performed a systematic review to gather data on length of stay (LoS) of patients with COVID-19 in hospital and in ICU. We subsequently developed a method to generate LoS distributions which combines summary statistics reported in multiple studies, accounting for differences in sample sizes. Applying this approach we provide distributions for general hospital and ICU LoS from studies in China and elsewhere, for use by the community. Results We identified 52 studies, the majority from China (46/52). Median hospital LoS ranged from 4 to 53 days within China, and 4 to 21 days outside of China, across 45 studies. ICU LoS was reported by eight studies - four each within and outside China - with median values ranging from 6 to 12 and 4 to 19 days, respectively. Our summary distributions have a median hospital LoS of 14 (IQR: 10-19) days for China, compared with 5 (IQR: 3-9) days outside of China. For ICU, the summary distributions are more similar (median (IQR) of 8 (5-13) days for China and 7 (4-11) days outside of China). There was a visible difference by discharge status, with patients who were discharged alive having longer LoS than those who died during their admission, but no trend associated with study date. Conclusion Patients with COVID-19 in China appeared to remain in hospital for longer than elsewhere. This may be explained by differences in criteria for admission and discharge between countries, and different timing within the pandemic. In the absence of local data, the combined summary LoS distributions provided here can be used to model bed demands for contingency planning and then updated, with the novel method presented here, as more studies with aggregated statistics emerge outside China.

Additional file 1 List of search terms. Supplementary Table A. Description of information extracted from included studies. Fig SA: LoS by disease severity. Fig SB: LoS by study median age. Fig SC: LoS by outcome status. Fig SD: Summary distributions for China/other and total/ICU. Fig SE: Sensitivity of length of stay (LoS) with and without overlapping populations removed. Fig SF: Sensitivity analysis of summary distributions to weighting.