Genomic epidemiology demonstrates spatially clustered, local transmission of Plasmodium falciparum in forest-going populations in southern Lao PDR.

While there has been significant progress in controlling falciparum malaria in the Lao People's Democratic Republic (PDR), sporadic cases persist in southern provinces where the extent and patterns of transmission remain largely unknown. To assess parasite transmission in this area, 53 Plasmodium falciparum (Pf) positive cases detected through active test and treat campaigns from December 2017 to November 2018 were sequenced, targeting 204 highly polymorphic amplicons. Two R packages, MOIRE and Dcifer, were applied to assess the multiplicity of infections (MOI), effective MOI (eMOI), within-host parasite relatedness, and between-host parasite relatedness ([Formula: see text]). Genomic data were integrated with survey data to characterize the temporal and spatial structures of identified clusters. The positive cases were mainly captured during the focal test and treat campaign conducted in 2018, and in the Pathoomphone area, which had the highest test positivity and forest activity. About 30% of the cases were polyclonal infections, with over half of theses (63%) showing within-host relatedness greater than 0.6, suggesting that cotransmission rather than superinfection was primarily responsible for maintaining polyclonality. A large majority of cases (81%) were infected by parasites genetically linked to one or more other cases. We identified five genetically distinct clusters in forest fringe villages within the Pathoomphone district, characterized by a high degree of genetic relatedness between parasites (mean [Formula: see text] = 0.8). Four smaller clusters of 2-3 cases linked Moonlapamok and Pathoomphone districts, with an average [Formula: see text] of 0.6, suggesting cross-district transmission. Most of the clustered cases occurred within 20 km and 2 months of each other, consistent with focal transmission. Transmission clusters identified in this study confirm the role of ongoing focal parasite transmission occurring within the forest or forest-fringe in the highly mobile population.

Optimizing the implementation of a participant-collected, mail-based SARS-CoV-2 serological survey in university-affiliated populations: lessons learned and practical guidance.

The rapid spread of SARS-CoV-2 is largely driven by pre-symptomatic or mildly symptomatic individuals transmitting the virus. Serological tests to identify antibodies against SARS-CoV-2 are important tools to characterize subclinical infection exposure.During the summer of 2020, a mail-based serological survey with self-collected dried blood spot (DBS) samples was implemented among university affiliates and their household members in Massachusetts, USA. Described are challenges faced and novel procedures used during the implementation of this study to assess the prevalence of SARS-CoV-2 antibodies amid the pandemic.Important challenges included user-friendly remote and contact-minimized participant recruitment, limited availability of some commodities and laboratory capacity, a potentially biased sample population, and policy changes impacting the distribution of clinical results to study participants. Methods and lessons learned to surmount these challenges are presented to inform design and implementation of similar sero-studies.This study design highlights the feasibility and acceptability of self-collected bio-samples and has broad applicability for other serological surveys for a range of pathogens. Key lessons relate to DBS sampling, supply requirements, the logistics of packing and shipping packages, data linkages to enrolled household members, and the utility of having an on-call nurse available for participant concerns during sample collection. Future research might consider additional recruitment techniques such as conducting studies during academic semesters when recruiting in a university setting, partnerships with supply and shipping specialists, and using a stratified sampling approach to minimize potential biases in recruitment.

Civilian-military malaria outbreak response in Thailand: an example of multi-stakeholder engagement for malaria elimination.

BACKGROUND: In April 2017, the Thai Ministry of Public Health (MoPH) was alerted to a potential malaria outbreak among civilians and military personnel in Sisaket Province, a highly forested area bordering Cambodia. The objective of this study was to present findings from the joint civilian-military outbreak response. METHODS: A mixed-methods approach was used to assess risk factors among cases reported during the 2017 Sisaket malaria outbreak. Routine malaria surveillance data from January 2013 to March 2018 obtained from public and military medical reporting systems and key informant interviews (KIIs) (n = 72) were used to develop hypotheses about potential factors contributing to the outbreak. Joint civilian-military response activities included entomological surveys, mass screen and treat (MSAT) and vector control campaigns, and scale-up of the "1-3-7" reactive case detection approach among civilians alongside a pilot "1-3-7" study conducted by the Royal Thai Army (RTA). RESULTS: Between May-July 2017, the monthly number of MoPH-reported cases surpassed the epidemic threshold. Outbreak cases detected through the MoPH mainly consisted of Thai males (87%), working as rubber tappers (62%) or military/border police (15%), and Plasmodium vivax infections (73%). Compared to cases from the previous year (May-July 2016), outbreak cases were more likely to be rubber tappers (OR = 14.89 [95% CI: 5.79-38.29]; p < 0.001) and infected with P. vivax (OR=2.32 [1.27-4.22]; p = 0.006). Themes from KIIs were congruent with findings from routine surveillance data. Though limited risk factor information was available from military cases, findings from RTA's "1-3-7" study indicated transmission was likely occurring outside military bases. Data from entomological surveys and MSAT campaigns support this hypothesis, as vectors were mostly exophagic and parasite prevalence from MSAT campaigns was very low (range: 0-0.7% by PCR/microscopy). CONCLUSIONS: In 2017, an outbreak of mainly P. vivax occurred in Sisaket Province, affecting mainly military and rubber tappers. Vector control use was limited to the home/military barracks, indicating that additional interventions were needed during high-risk forest travel periods. Importantly, this outbreak catalyzed joint civilian-military collaborations and integration of the RTA into the national malaria elimination strategy (NMES). The Sisaket outbreak response serves as an example of how civilian and military public health systems can collaborate to advance national malaria elimination goals in Southeast Asia and beyond.

The impact of transfluthrin on the spatial repellency of the primary malaria mosquito vectors in Vietnam: Anopheles dirus and Anopheles minimus.

BACKGROUND: The complexity of mosquito-borne diseases poses a major challenge to global health efforts to mitigate their impact on people residing in sub-tropical and tropical regions, to travellers and deployed military personnel. To supplement drug- and vaccine-based disease control programmes, other strategies are urgently needed, including the direct control of disease vectors. Modern vector control research generally focuses on identifying novel active ingredients and/or innovative methods to reduce human-mosquito interactions. These efforts include the evaluation of spatial repellents, which are compounds capable of altering mosquito feeding behaviour without direct contact with the chemical source. METHODS: This project examined the impact of airborne transfluthrin from impregnated textile materials on two important malaria vectors, Anopheles dirus and Anopheles minimus. Repellency was measured by movement within taxis cages within a semi-field environment at the National Institute of Hygiene and Epidemiology in Hanoi, Vietnam. Knockdown and mortality were measured in adult mosquito bioassay cages. Metered-volume air samples were collected at a sub-set of points in the mosquito exposure trial. RESULTS: Significant differences in knockdown/mortality were observed along a gradient from the exposure source with higher rates of knockdown/mortality at 2 m and 4 m when compared with the furthest distance (16 m). Knockdown/mortality was also greater at floor level and 1.5 m when compared to 3 m above the floor. Repellency was not significantly different except when comparing 2 m and 16 m taxis cages. Importantly, the two species reacted differently to transfluthrin, with An. minimus being more susceptible to knockdown and mortality. The measured concentrations of airborne transfluthrin ranged from below the limit of detection to 1.32 ng/L, however there were a limited number of evaluable samples complicating interpretation of these results. CONCLUSIONS: This study, measuring repellency, knockdown and mortality in two malaria vectors in Vietnam demonstrates that both species are sensitive to airborne transfluthrin. The differences in magnitude of response between the two species requires further study before use in large-scale vector control programmes to delineate how spatial repellency would impact the development of insecticide resistance and the disruption of biting behaviour.

Prevalence and risk factors for asymptomatic malaria and genotyping of glucose 6-phosphate (G6PD) deficiencies in a vivax-predominant setting, Lao PDR: implications for sub-national elimination goals.

BACKGROUND: Lao People Democratic Republic (PDR; Laos), a landlocked country in Southeast Asia, has made important progress in reducing malaria morbidity and mortality in the past 5-6 years, and the northern provinces have very low reported incidence. To support national progress towards elimination, it is critical to verify and understand these changes in disease burden. METHODS: A two-stage cluster cross-sectional survey was conducted in four districts within four northern provinces (Khua, Phongsaly Province; Paktha, Bokeo Province; Nambak, Luang Prabang, and Muang Et, Huaphanh Province). During September and October 2016, demographics and malaria risk factors were collected from a total of 1492 households. A total of 5085 persons consented to collection of blood samples for testing, by rapid diagnostic test (RDT) and polymerase chain reaction (PCR)-based testing. Risk factors for infection were examined using logistic regression; and a randomized subset of males was tested for glucose-6-phosphate dehydrogenase (G6PD) deficiencies using a combined PCR and sequencing approach. RESULTS: There were zero positives by RDT, and PCR detected Plasmodium infections in 39 (0.77%; 95% CI 0.40-1.47%) of 5082 analysable samples. The species distribution was Plasmodium vivax (28 total); Plasmodium falciparum/P. vivax (5); P. falciparum (3), Plasmodium malariae (2), and P. vivax/P. malariae (1). In multivariable analysis, the main risk factors included having any other cases within the household [aOR 12.83 (95% CI 4.40 to 37.38), p < 0.001]; and lack of bed net ownership within the household [aOR 10.91 (95% 5.42-21.94), p < 0.001]; age, sex and forest-travel were not associated with parasitaemia. A total of 910 males were tested for the six most common G6PDd in SE Asia; and 30 (3.3%; 95% CI 2.1-5.1%) had a G6PD variant allele associated with G6PD deficiency, with the majority being the Union (14) and Viangchan (11) polymorphisms, with smaller numbers of Canton and Mahidol. CONCLUSION: This is the first rigorous PCR-based population survey for malaria infection in Northern Lao PDR, and found a very low prevalence of asymptomatic Plasmodium infections by standard PCR methods, with P. vivax predominating in the surveyed districts. Clustering of cases within households, and lack of a bed nets suggest reactive case detection, and scale-up of coverage should be prioritized. The predominance of infections with P. vivax, combined with moderate levels of serious G6PD deficiencies highlight the need for careful rollout of primaquine towards elimination goals.

Characterization of Plasmodium falciparum and Plasmodium vivax recent exposure in an area of significantly decreased transmission intensity in Central Vietnam.

BACKGROUND: In Vietnam, malaria transmission has been reduced to very low levels over the past 20 years, and as a consequence, the country aims to eliminate malaria by 2030. This study aimed to characterize the dynamics and extent of the parasite reservoir in Central Vietnam, in order to further target elimination strategies and surveillance. METHODS: A 1-year prospective cohort study (n = 429) was performed in three rural communities in Quang Nam province. Six malaria screenings were conducted between November 2014 and November 2015, including systematic clinical examination and blood sampling for malaria parasite identification, as well as molecular and serological analysis of the study population. Malaria infections were detected by light microscopy (LM) and quantitative real time PCR (qPCR), while exposure to Plasmodium falciparum and Plasmodium vivax was measured in the first and last survey by ELISA for PfAMA1, PfGLURP R2, PvAMA1, and PvMSP1-19. Classification and regression trees were used to define seropositivity and recent exposure. RESULTS: Four malaria infections (2 P. falciparum, 2 P. vivax) were detected in the same village by qPCR and/or LM. No fever cases were attributable to malaria. At the same time, the commune health centre (serving a larger area) reported few cases of confirmed malaria cases. Nevertheless, serological data proved that 13.5% of the surveyed population was exposed to P. falciparum and/or P. vivax parasites during the study period, of which 32.6% were seronegative at the start of the study, indicating ongoing transmission in the area. Risk factor analysis for seroprevalence and exposure to P. falciparum and/or P. vivax identified structural or economic risk factors and activity/behaviour-related factors, as well as spatial heterogeneity at the village level. CONCLUSIONS: Previous studies in Central Vietnam demonstrated high occurrence of asymptomatic and sub-microscopic infections. However, in this study very few asymptomatic infections were detected despite serological evidence of continued transmission. Nonetheless, the factors associated with spatial heterogeneity in transmission could be evaluated using serological classification of recent exposure, which supports the usefulness of serological methods to monitor malaria transmission.

Regional initiatives for malaria elimination: Building and maintaining partnerships.

Andrew Lover and colleagues discuss regional malaria initiatives, the strengths and challenges.

Eliminate now: seven critical actions required to accelerate elimination of Plasmodium falciparum malaria in the Greater Mekong Subregion.

The emergence in 2009 of Plasmodium falciparum parasites resistant to the primary therapies currently in use (artemisinin-based combination therapy, ACT) in Southeast Asia threatens to set back decades of global progress in malaria control and elimination. Progress to date through multiple sets of initiatives and partners to contain or eliminate these parasites has been hampered due to a wide range of organizational, financial, and health systems-level challenges. In this commentary, a set of seven specific and concrete actions are proposed to directly address these issues and to accelerate P. falciparum elimination within the Greater Mekong Subregion to avert a wider public health crisis. These actions are specifically needed to elevate the situation and response mechanisms to those of a true emergency; to address systems-level challenges with personnel limitations and stock-outs of key commodities; and to restructure the response mechanisms to be well-aligned with the required outcomes. Consideration of these issues is especially pressing with planning meetings for renewal of the Regional Artemisinin-resistance Initiative (RAI) framework slated for late 2016 and into 2017, but these suggestions are also relevant for malaria programmes globally.

Early diagnosis of dengue disease severity in a resource-limited Asian country.

BACKGROUND: Dengue is endemic throughout Cambodia, a country faced with significant health and economic challenges. We undertook a clinical study at the National Paediatric Hospital in Phnom Penh to evaluate clinical diagnostic parameters for dengue and predictors of disease outcome. METHODS: Between September 2011 and January 2013, all consecutive inpatients aged between 1 and 15 years and presenting with suspected dengue were enrolled. They were clinically assessed using both the 1997 and 2009 WHO dengue classifications. Specimens were collected upon admission and discharge and tested for dengue at Institut Pasteur in Cambodia. RESULTS: A total of 701 patients were screened. Of these, 79 % were dengue-confirmed by laboratory testing, and 21 % tested dengue-negative. A positive tourniquet test, absence of upper respiratory symptoms, leukopenia, thrombocytopenia, and elevated liver transaminases were independent predictors for laboratory-confirmed dengue among the children. The presence of several warning signs on hospital admission was associated with a concurrent laboratory-confirmed diagnosis of severe disease outcome. CONCLUSIONS: The presence of two or more warning signs was associated with a concurrent laboratory-confirmed diagnosis of severe dengue at hospital admission. Thus, a cumulative score combining simple clinical parameters and first-line laboratory findings could be used to accurately predict dengue virus infection in pediatric populations, optimizing triage in settings with limited laboratory resources.

The distribution of incubation and relapse times in experimental human infections with the malaria parasite Plasmodium vivax.

BACKGROUND: The distributions of incubation and relapse periods are key components of infectious disease models for the malaria parasite Plasmodium vivax; however, detailed distributions based upon experimental data are lacking. METHODS: Using a range of historical, experimental mosquito-transmitted human infections, Bayesian estimation with non-informative priors was used to determine parametric distributions that can be readily implemented for the incubation period and time-to-first relapse in P. vivax infections, including global subregions by parasite source. These analyses were complemented with a pooled analysis of observational human infection data with infections that included malaria chemoprophylaxis and long-latencies. The epidemiological impact of these distributional assumptions was explored using stochastic epidemic simulations at a fixed reproductive number while varying the underlying distribution of incubation periods. RESULTS: Using the Deviance Information Criteria to compare parameterizations, experimental incubation periods are most closely modeled with a shifted log-logistic distribution; a log-logistic mixture is the best fit for incubations in observational studies. The mixture Gompertz distribution was the best fit for experimental times-to-relapse among the tested parameterizations, with some variation by geographic subregions. Simulations suggest underlying distributional assumptions have critically important impacts on both the time-scale and total case counts within epidemics. CONCLUSIONS: These results suggest that the exponential and gamma distributions commonly used for modeling incubation periods and relapse times inadequately capture the complexity in the distributions of event times in P. vivax malaria infections. In future models, log-logistic and Gompertz distributions should be utilized for general incubation periods and relapse times respectively, and region-specific distributions should be considered to accurately model and predict the epidemiology of this important human pathogen.

Re-assessing the relationship between sporozoite dose and incubation period in Plasmodium vivax malaria: a systematic re-analysis.

Infections with the malaria parasite Plasmodium vivax are noteworthy for potentially very long incubation periods (6-9 months), which present a major barrier to disease elimination. Increased sporozoite challenge has been reported to be associated with both shorter incubation and pre-patent periods in a range of human challenge studies. However, this evidence base has scant empirical foundation, as these historical analyses were limited by available analytic methods, and provides no quantitative estimates of effect size. Following a comprehensive literature search, we re-analysed all identified studies using survival and/or logistic models plus contingency tables. We have found very weak evidence for dose-dependence at entomologically plausible inocula levels. These results strongly suggest that sporozoite dosage is not an important driver of long-latency. Evidence presented suggests that parasite strain and vector species have quantitatively greater impacts, and the potential existence of a dose threshold for human dose-response to sporozoites. Greater consideration of the complex interplay between these aspects of vectors and parasites are important for human challenge experiments, vaccine trials, and epidemiology towards global malaria elimination.

Spatial epidemiology and climatic predictors of paediatric dengue infections captured via sentinel site surveillance, Phnom Penh Cambodia 2011-2012.

BACKGROUND: Dengue is a major contributor to morbidity in children aged twelve and below throughout Cambodia; the 2012 epidemic season was the most severe in the country since 2007, with more than 42,000 reported (suspect or confirmed) cases. METHODS: We report basic epidemiological characteristics in a series of 701 patients at the National Paediatric Hospital in Cambodia, recruited during a prospective clinical study (2011-2012). To more fully explore this cohort, we examined climatic factors using multivariate negative binomial models and spatial clustering of cases using spatial scan statistics to place the clinical study within a larger epidemiological framework. RESULTS: We identify statistically significant spatial clusters at the urban village scale, and find that the key climatic predictors of increasing cases are weekly minimum temperature, median relative humidity, but find a negative association with rainfall maximum, all at lag times of 1-6 weeks, with significant effects extending to 10 weeks. CONCLUSIONS: Our results identify clustering of infections at the neighbourhood scale, suggesting points for targeted interventions, and we find that the complex interactions of vectors and climatic conditions in this setting may be best captured by rising minimum temperature, and median (as opposed to mean) relative humidity, with complex and limited effects from rainfall. These results suggest that real-time cluster detection during epidemics should be considered in Cambodia, and that improvements in weather data reporting could benefit national control programs by allow greater prioritization of limited health resources to both vulnerable populations and time periods of greatest risk. Finally, these results add to the increasing body of knowledge suggesting complex interactions between climate and dengue cases that require further targeted research.

Measuring effects of ivermectin-treated cattle on potential malaria vectors in Vietnam: A cluster-randomized trial.

BACKGROUND: Malaria elimination using current tools has stalled in many areas. Ivermectin (IVM) is a broad-antiparasitic drug and mosquitocide and has been proposed as a tool for accelerating progress towards malaria elimination. Under laboratory conditions, IVM has been shown to reduce the survival of adult Anopheles populations that have fed on IVM-treated mammals. Treating cattle with IVM has been proposed as an important contribution to malaria vector management, however, the impacts of IVM in this One Health use case have been untested in field trials in Southeast Asia. METHODS: Through a randomized village-based trial, this study quantified the effect of IVM-treated cattle on anopheline populations in treated vs. untreated villages in Central Vietnam. Local zebu cattle in six rural villages were included in this study. In three villages, cattle were treated with IVM at established veterinary dosages, and in three additional villages cattle were left as untreated controls. For the main study outcome, the mosquito populations in all villages were sampled using cattle-baited traps for six nights before, and six nights after a 2-day IVM-administration (intervention) period. Anopheline species were characterized using taxonomic keys. The impact of the intervention was analyzed using a difference-in-differences (DID) approach with generalized estimating equations (with negative binomial distribution and robust errors). This intervention was powered to detect a 50% reduction in total nightly Anopheles spp. vector catches from cattle-baited traps. Given the unusual diversity in anopheline populations, exploratory analyses examined taxon-level differences in the ecological population diversity. RESULTS: Across the treated villages, 1,112 of 1,523 censused cows (73% overall; range 67% to 83%) were treated with IVM. In both control and treated villages, there was a 30% to 40% decrease in total anophelines captured in the post-intervention period as compared to the pre-intervention period. In the control villages, there were 1,873 captured pre-intervention and 1,079 captured during the post-intervention period. In the treated villages, there were 1,594 captured pre-intervention, and 1,101 captured during the post-intervention period. The difference in differences model analysis comparing total captures between arms was not statistically significant (p = 0.61). Secondary outcomes of vector population diversity found that in three villages (one control and two treatment) Brillouin's index increased, and in three villages (two control and one treatment) Brillouin's index decreased. When examining biodiversity by trapping-night, there were no clear trends in treated or untreated vector populations. Additionally, there were no clear trends when examining the components of biodiversity: richness and evenness. CONCLUSIONS: The ability of this study to quantify the impacts of IVM treatment was limited due to unexpectedly large spatiotemporal variability in trapping rates; an area-wide decrease in trapping counts across all six villages post-intervention; and potential spillover effects. However, this study provides important data to directly inform future studies in the GMS and beyond for IVM-based vector control.

Syndromic surveillance of population-level COVID-19 burden with cough monitoring in a hospital emergency waiting room.

Syndromic surveillance is an effective tool for enabling the timely detection of infectious disease outbreaks and facilitating the implementation of effective mitigation strategies by public health authorities. While various information sources are currently utilized to collect syndromic signal data for analysis, the aggregated measurement of cough, an important symptom for many illnesses, is not widely employed as a syndromic signal. With recent advancements in ubiquitous sensing technologies, it becomes feasible to continuously measure population-level cough incidence in a contactless, unobtrusive, and automated manner. In this work, we demonstrate the utility of monitoring aggregated cough count as a syndromic indicator to estimate COVID-19 cases. In our study, we deployed a sensor-based platform (Syndromic Logger) in the emergency room of a large hospital. The platform captured syndromic signals from audio, thermal imaging, and radar, while the ground truth data were collected from the hospital's electronic health record. Our analysis revealed a significant correlation between the aggregated cough count and positive COVID-19 cases in the hospital (Pearson correlation of 0.40, p-value < 0.001). Notably, this correlation was higher than that observed with the number of individuals presenting with fever (ρ = 0.22, p = 0.04), a widely used syndromic signal and screening tool for such diseases. Furthermore, we demonstrate how the data obtained from our Syndromic Logger platform could be leveraged to estimate various COVID-19-related statistics using multiple modeling approaches. Aggregated cough counts and other data, such as people density collected from our platform, can be utilized to predict COVID-19 patient visits related metrics in a hospital waiting room, and SHAP and Gini feature importance-based metrics showed cough count as the important feature for these prediction models. Furthermore, we have shown that predictions based on cough counting outperform models based on fever detection (e.g., temperatures over 39°C), which require more intrusive engagement with the population. Our findings highlight that incorporating cough-counting based signals into syndromic surveillance systems can significantly enhance overall resilience against future public health challenges, such as emerging disease outbreaks or pandemics.

Quantifying effect of geographic location on epidemiology of Plasmodium vivax malaria.

Recent autochthonous transmission of Plasmodium vivax malaria in previously malaria-free temperate regions has generated renewed interest in the epidemiology of this disease. Accurate estimates of the incubation period and time to relapse are required for effective malaria surveillance; however, this information is currently lacking. By using historical data from experimental human infections with diverse P. vivax strains, survival analysis models were used to obtain quantitative estimates of the incubation period and time to first relapse for P. vivax malaria in broad geographic regions. Results show that Eurasian strains from temperate regions have longer incubation periods, and Western Hemisphere strains from tropical and temperate regions have longer times to relapse compared with Eastern Hemisphere strains. The diversity in these estimates of key epidemiologic parameters for P. vivax supports the need for elucidating local epidemiology to inform clinical follow-up and to build an evidence base toward global elimination of malaria.

Progression from new methicillin-resistant Staphylococcus aureus colonisation to infection: an observational study in a hospital cohort.

BACKGROUND: Patients newly colonised with methicillin-resistant Staphylococcus aureus (MRSA) are at higher risk of clinical MRSA infection. At present, there are limited data on the duration or magnitude of this risk in a hospital population with a known time of MRSA acquisition. METHODS: A retrospective cohort study of 909 adult patients known to have newly identified MRSA colonisation during admission to National University Hospital, Singapore between 1 July 2007 and 30 June 2011 was undertaken. Patients were excluded if they had history of previous MRSA colonisation or infection, or if they had been a hospital inpatient in the preceding 12 months. Data were collected on the development of MRSA infection requiring hospitalisation up to 30 June 2012. RESULTS: Of 840 patients newly colonised with MRSA as identified on active surveillance and not clinical specimens, 546 were men (65.0%) and the median age was 65 years (range 18-103 years). Median follow up was 24 months (range 0 -64 months, 85.1% followed >6 months). Clinical infection occurred in 121 patients (14.4%) with median time to infection of 22 days (95% CI 14-31). Overall 71.9% (87/121) of infected patients developed infection within 60 days of the date MRSA colonisation was detected. However, 17/121 patients (14.0%) developed clinical infection more than six months after documented MRSA acquisition. The most common sites of clinical infection were skin and soft tissue (49/121, 40.5%, 95% CI 31.7-49.8), respiratory tract (37/121, 30.6%, 95% CI 22.5-39.6) and bone and joint infections (14/121, 11.6%, 95% CI 6.5-18.7). Thirteen patients (13/121, 10.7%, 95% CI 5.8-17.7) had bacteraemias, of which six (5.0% 95% CI 1.8-10.5) were primary and seven (5.7%, 95% CI 2.3-11.6) were secondary to infection at other sites. Crude mortality at 30 days and six months was higher in patients with MRSA infection than colonisation alone (aOR 5.49, 95% CI 2.75-10.95, p<0.001 and aOR 2.94, 95% CI 1.78-4.85, p<0.001 respectively). CONCLUSION: Risk of clinical infection is highest soon after MRSA acquisition. Prevention of MRSA acquisition in hospital will have significant impact on morbidity and mortality for patients.

Knowledge, attitudes, and practices regarding COVID-19 among university students and employees in Massachusetts, USA: A qualitative study.

OBJECTIVE: To explore the knowledge, attitudes, and practices regarding COVID-19 in university affiliates to inform future COVID-19 policies and practices. PARTICIPANTS: Undergraduate students, graduate students and university employees at a large public university. METHODS: Semi-structured focus groups and interviews were conducted between December 2020 and January 2021. Data were analyzed via inductive thematic analysis. RESULTS: Analysis of data from the 36 participants generated five themes: COVID-19 knowledge, stress and coping, trust, decision-making, and institutional feedback. Misunderstanding of COVID-19 preventive behaviors was common, which appeared to compound high levels of stress and presented an educational opportunity. University investment in an asymptomatic testing program was reported to increase perceived safety. CONCLUSIONS: Participants' experiences with a large university's COVID-19 response suggest a desire for consistent and transparent communication and an opportunity for institutions to examine the effectiveness of their communication strategies, public health protocols, and mechanisms for assessing and mitigating stress.

Passive Monitoring of Crowd-Level Cough Counts in Waiting Areas produces Reliable Syndromic Indicator for Total COVID-19 Burden in a Hospital Emergency Clinic.

Syndromic surveillance is an effective tool for enabling the timely detection of infectious disease outbreaks and facilitating the implementation of effective mitigation strategies by public health authorities. While various information sources are currently utilized to collect syndromic signal data for analysis, the aggregated measurement of cough, an important symptom for many illnesses, is not widely employed as a syndromic signal. With recent advancements in ubiquitous sensing technologies, it becomes feasible to continuously measure population-level cough incidence in a contactless, unobtrusive, and automated manner. In this work, we demonstrate the utility of monitoring aggregated cough count as a syndromic indicator to estimate COVID-19 cases. In our study, we deployed a sensor-based platform (Syndromic Logger) in the emergency room of a large hospital. The platform captured syndromic signals from audio, thermal imaging, and radar, while the ground truth data were collected from the hospital's electronic health record. Our analysis revealed a significant correlation between the aggregated cough count and positive COVID-19 cases in the hospital (Pearson correlation of 0.40, p-value < 0.001). Notably, this correlation was higher than that observed with the number of individuals presenting with fever (ρ = 0.22, p = 0.04), a widely used syndromic signal and screening tool for such diseases. Furthermore, we demonstrate how the data obtained from our Syndromic Logger platform could be leveraged to estimate various COVID-19-related statistics using multiple modeling approaches. Our findings highlight the efficacy of aggregated cough count as a valuable syndromic indicator associated with the occurrence of COVID-19 cases. Incorporating this signal into syndromic surveillance systems for such diseases can significantly enhance overall resilience against future public health challenges, such as emerging disease outbreaks or pandemics.

Quantifying the Relationship between SARS-CoV-2 Wastewater Concentrations and Building-Level COVID-19 Prevalence at an Isolation Residence: A Passive Sampling Approach.

SARS-CoV-2 RNA loads can be detected in the excreta of individuals with COVID-19 and have demonstrated positive correlations with clinical infection trends. Consequently, wastewater-based epidemiology (WBE) approaches have been implemented globally as a public health surveillance tool to monitor community-level prevalence of infections. The majority of wastewater specimens are gathered as either composite samples via automatic samplers (autosamplers) or grab samples. However, autosamplers are expensive and can be challenging to maintain in cold weather, while grab samples are particularly susceptible to temporal variation when sampling sewage directly from complex matrices outside residential buildings. Passive sampling can provide an affordable, practical, and scalable sampling system while maintaining a reproducible SARS-CoV-2 signal. In this regard, we deployed tampons as passive samplers outside of a COVID-19 isolation unit (a segregated residence hall) at a university campus from 1 February 2021-21 May 2021. Samples (n = 64) were collected 3-5 times weekly and remained within the sewer for a median duration of 24 h. SARS-CoV-2 RNA was quantified using reverse-transcription quantitative polymerase chain reaction (RT-qPCR) targeting the N1 and N2 gene fragments. We quantified the mean viral load captured per individual and the association between the daily viral load and total persons, adjusting for covariates using multivariable models to provide a baseline estimate of viral shedding. Samples were processed through two distinct laboratory pipelines on campus, yielding highly correlated N2 concentrations. Data obtained here highlight the success of passive sampling utilizing tampons to capture SARS-CoV-2 in wastewater coming from a COVID-19 isolation residence, indicating that this method can help inform building-level public health responses.

Quantifying the relationship between SARS-CoV-2 wastewater concentrations and building-level COVID-19 prevalence at an isolation residence using a passive sampling approach.

SARS-CoV-2 RNA can be detected in the excreta of individuals with COVID-19 and has demonstrated a positive correlation with various clinical parameters. Consequently, wastewater-based epidemiology (WBE) approaches have been implemented globally as a public health surveillance tool to monitor the community-level prevalence of infections. Over 270 higher education campuses monitor wastewater for SARS-CoV-2, with most gathering either composite samples via automatic samplers (autosamplers) or grab samples. However, autosamplers are expensive and challenging to manage with seasonal variability, while grab samples are particularly susceptible to temporal variation when sampling sewage directly from complex matrices outside residential buildings. Prior studies have demonstrated encouraging results utilizing passive sampling swabs. Such methods can offer affordable, practical, and scalable alternatives to traditional methods while maintaining a reproducible SARS-CoV-2 signal. In this regard, we deployed tampons as passive samplers outside of a COVID-19 isolation unit (a segregated residence hall) at a university campus from February 1, 2021 â€" May 21, 2021. Samples were collected several times weekly and remained within the sewer for a minimum of 24 hours (n = 64). SARS-CoV-2 RNA was quantified using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) targeting the viral N1 and N2 gene fragments. We quantified the mean viral load captured per individual and the association between the daily viral load and total persons, adjusting for covariates using multivariable models to provide a baseline estimate of viral shedding. Samples were processed through two distinct laboratory pipelines on campus, yielding highly correlated N2 concentrations. Data obtained here highlight the success of passive sampling utilizing tampons to capture SARS-CoV-2 in wastewater coming from a COVID-19 isolation residence, indicating that this method can help inform public health responses in a range of settings. Highlights: Daily SARS-CoV-2 RNA loads in building-level wastewater were positively associated with the total number of COVID-19 positive individuals in the residenceThe variation in individual fecal shedding rates of SARS-CoV-2 extended four orders of magnitudeWastewater sample replicates were highly correlated using distinct processing pipelines in two independent laboratoriesWhile the isolation residence was occupied, SARS-CoV-2 RNA was detected in all passive samples.