A systematic review of the data, methods and environmental covariates used to map Aedes-borne arbovirus transmission risk.

BACKGROUND: Aedes (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 different Aedes-borne arboviruses from local to global scales, identifying differences and similarities in the data types, covariates, and modelling approaches used. METHODS: We 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.). RESULTS: We found a growing number of arbovirus risk mapping studies across all endemic regions and arboviral diseases, with a total of 176 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%, 31/144) robustly tested combinations of covariates from different domains (e.g. climatic, sociodemographic, ecological, etc.) and only 49% of studies assessed predictive performance via out-of-sample validation procedures. CONCLUSIONS: Here we show that approaches to map risk for different arboviruses have diversified in response to changing use cases, epidemiology and data availability. We identify key differences in mapping approaches between different arboviral diseases, discuss future research needs and outline specific recommendations for future arbovirus mapping.

The burden and dynamics of hospital-acquired SARS-CoV-2 in England.

Hospital-based transmission had a dominant role in Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus (SARS-CoV) epidemics1,2, 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 estimate that between June 2020 and March 2021 between 95,000 and 167,000 inpatients acquired SARS-CoV-2 in hospitals (1% to 2% of all hospital admissions in this period). Analysis of time series data provided evidence that patients who themselves acquired SARS-CoV-2 infection in hospital were the main sources of transmission to other patients. Increased transmission to inpatients 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 unrecognized 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.

A phylogenetic study of dengue virus in urban Vietnam shows long-term persistence of endemic strains.

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.

The contribution of hospital-acquired infections to the COVID-19 epidemic in England in the first half of 2020.

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.

The contribution of hospital-acquired infections to the COVID-19 epidemic in England in the first half of 2020.

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 31 st 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.

Use of and barriers to maternal health services in southeast Chad: results of a population-based survey 2019.

OBJECTIVES: Chad 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. DESIGN: Retrospective 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. SETTING: We interviewed women in selected households in Sila region in 2019. PARTICIPANTS: Women at reproductive age, who have given birth in the previous 2 years and are living in Koukou Angarana and Goz Beida district. PRIMARY OUTCOMES: Use of and access barriers to MHS including antenatal care (ANC), delivery care in a health facility (DC), postnatal care (PNC) and contraceptive methods. RESULTS: In 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. CONCLUSION: In 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.

Effectiveness of infection prevention and control interventions, excluding personal protective equipment, to prevent nosocomial transmission of SARS-CoV-2: a systematic review and call for action.

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.

Case-area targeted interventions (CATI) for reactive dengue control: Modelling effectiveness of vector control and prophylactic drugs in Singapore.

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.

COVID-19 length of hospital stay: a systematic review and data synthesis.

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 of early evidence 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 total 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.

Poor Reporting of Outcomes Beyond Accuracy in Point-of-Care Tests for Syphilis: A Call for a Framework.

Background. Point-of-care (POC) diagnostics for syphilis can contribute to epidemic control by offering a timely knowledge of serostatus. Although accuracy data on POC syphilis tests have been widely published, few studies have evaluated broader outcomes beyond accuracy that impact patients and health systems. We comprehensively reviewed evidence and reporting of these implementation research outcomes (IROs), and proposed a framework to improve their quality. Methods. Three reviewers systematically searched 6 electronic databases from 1980 to 2014 for syphilis POC studies reporting IROs. Data were abstracted and findings synthesised narratively. Results. Of 71 studies identified, 38 documented IROs. IROs were subclassified into preference (7), acceptability (15), feasibility (15), barriers and challenges (15), impact (13), and prevalence (23). Using our framework and definitions, a pattern of incomplete documentation, inconsistent definitions, and lack of clarity was identified across all IROs. Conclusion. Although POC screening tests for syphilis were generally favourably evaluated across a range of outcomes, the quality of evidence was compromised by inconsistent definitions, poor methodology, and documentation of outcomes. A framework for standardized reporting of outcomes beyond accuracy was proposed and considered a necessary first step towards an effective implementation of these metrics in POC diagnostics research.

Are Treponema pallidum specific rapid and point-of-care tests for syphilis accurate enough for screening in resource limited settings? Evidence from a meta-analysis.

BACKGROUND: Rapid and point-of-care (POC) tests for syphilis are an invaluable screening tool, yet inadequate evaluation of their diagnostic accuracy against best reference standards limits their widespread global uptake. To fill this gap, a systematic review and meta-analysis was conducted to evaluate the sensitivity and specificity of rapid and POC tests in blood and serum samples against Treponema pallidum (TP) specific reference standards. METHODS: Five electronic databases (1980-2012) were searched, data was extracted from 33 articles, and Bayesian hierarchical models were fit. RESULTS: In serum samples, against a TP specific reference standard point estimates with 95% credible intervals (CrI) for the sensitivities of popular tests were: i) Determine, 90.04% (80.45, 95.21), ii) SD Bioline, 87.06% (75.67, 94.50), iii) VisiTect, 85.13% (72.83, 92.57), and iv) Syphicheck, 74.48% (56.85, 88.44), while specificities were: i) Syphicheck, 99.14% (96.37, 100), ii) Visitect, 96.45% (91.92, 99.29), iii) SD Bioline, 95.85% (89.89, 99.53), and iv) Determine, 94.15% (89.26, 97.66). In whole blood samples, sensitivities were: i) Determine, 86.32% (77.26, 91.70), ii) SD Bioline, 84.50% (78.81, 92.61), iii) Syphicheck, 74.47% (63.94, 82.13), and iv) VisiTect, 74.26% (53.62, 83.68), while specificities were: i) Syphicheck, 99.58% (98.91, 99.96), ii) VisiTect, 99.43% (98.22, 99.98), iii) SD Bioline, 97.95%(92.54, 99.33), and iv) Determine, 95.85% (92.42, 97.74). CONCLUSIONS: Rapid and POC treponemal tests reported sensitivity and specificity estimates comparable to laboratory-based treponemal tests. In resource limited settings, where access to screening is limited and where risk of patients lost to follow up is high, the introduction of these tests has already been shown to improve access to screening and treatment to prevent stillbirths and neonatal mortality due to congenital syphilis. Based on the evidence, it is concluded that rapid and POC tests are useful in resource limited settings with poor access to laboratories or screening for syphilis.

Accuracy of rapid and point-of-care screening tests for hepatitis C: a systematic review and meta-analysis.

BACKGROUND: 170 million persons worldwide are infected with hepatitis C, many of whom are undiagnosed. Although rapid diagnostic tests (RDTs) and point-of-care tests (POCTs) provide a time- and cost-saving alternative to conventional laboratory tests, their global uptake partly depends on their performance. PURPOSE: To meta-analyze the diagnostic accuracy of POCTs and RDTs to screen for hepatitis C. DATA SOURCES: MEDLINE, EMBASE, BIOSIS, and Web of Science (1992 to 2012) and bibliographies of included articles. STUDY SELECTION: All studies evaluating the diagnostic accuracy of POCTs and RDTs for hepatitis C in adults (aged ≥18 years). DATA EXTRACTION: Two independent reviewers extracted data and critiqued study quality. DATA SYNTHESIS: Of 19 studies reviewed, 18 were meta-analyzed and stratified by specimen type (whole blood, serum, plasma, or oral fluid) or test type (POCT or RDT). Sensitivity was similarly high in POCTs of whole blood (98.9% [95% CI, 94.5% to 99.8%]) and serum or plasma (98.9% [CI, 96.8% to 99.6%]), followed by RDTs of serum or plasma (98.4% [CI, 88.9% to 99.8%]) and POCTs of oral fluid (97.1% [CI, 94.7% to 98.4%]). Specificity was also high in POCTs of whole blood (99.5% [CI, 97.5% to 99.9%]) and serum or plasma (99.7% [CI, 99.3% to 99.9%]), followed by RDTs of serum or plasma (98.6% [CI, 94.9% to 99.6%]) and POCTs of oral fluid (98.2% [CI, 92.2% to 99.6%]). LIMITATION: Lack of data prevented sensitivity analyses of specific tests. CONCLUSION: Data suggest that POCTs of blood (serum, plasma, or whole blood) have the highest accuracy, followed by RDTs of serum or plasma and POCTs of oral fluids. Given their accuracy, convenience, and quick turnaround time, RDTs and POCTs may be useful in expanding first-line screening for hepatitis C. PRIMARY FUNDING SOURCE: Canadian Institutes of Health Research.

Rapid point-of-care first-line screening tests for hepatitis B infection: a meta-analysis of diagnostic accuracy (1980-2010).

OBJECTIVES: Three-hundred fifty million people worldwide are chronically infected with Hepatitis B, with four million acute infections annually. With infection concentrated in hard-to-reach populations and low resource settings, rapid point-of-care (POC) tests offer an efficient screening alternative to laboratory tests. We conducted a meta-analysis to evaluate accuracy of rapid POC tests screening for Hepatitis B. METHODS: Two reviewers searched four databases, critiqued quality. A hierarchical Bayesian meta-analysis correcting for imperfect reference standards was used. Based on components of the antigen-antibody response, 17 studies were stratified into three subgroups: (i) Hepatitis B surface antigen (HBsAg) tests; (ii) anti-HBsAg tests, and (iii) HBs+eAg tests. Further, we pooled estimates on individual tests with sufficient data. RESULTS: In subgroup 1, the pooled sensitivity (Sn) was 94.76% (95% credible interval (CrI): 90.08-98.23%) and specificity (Sp) was 99.54% (95% CrI: 99.03-99.95%). The Determine test reported a pooled Sn 98.2% (95% CrI: 94.7, 99.9) and Sp 99.9% (95% CrI: 99.3, 100); in subgroup 2, Sn 93.2% (95% CrI: 85.1, 98.5), Sp 93.1% (95% CrI: 81.9, 99.9); and in subgroup 3, the Binax test showed Sn 95.5% (95% CrI: 88.9, 99.4), Sp 99.8% (95% CrI: 99.3, 100). CONCLUSIONS: HBsAg tests, including Determine, and the HBs+eAg test, Binax showed high accuracy. Improvements in sensitivity of antibody-based tests will enhance their potential for global first-line screening.