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Michael Weekes

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Nick K. Jones1,2*, Lucy Rivett1,2*, Chris Workman3, Mark Ferris3, Ashley Shaw1, Cambridge COVID-19 Collaboration1,4, Paul J. Lehner1,4, Rob Howes5, Giles Wright3, Nicholas J. Matheson1,4,6¶, Michael P. Weekes1,7¶1 Cambridge University NHS Hospitals Foundation Trust, Cambridge, UK2 Clinical Microbiology & Public Health Laboratory, Public Health England, Cambridge, UK3 Occupational Health and Wellbeing, Cambridge Biomedical Campus, Cambridge, UK4 Cambridge Institute of Therapeutic Immunology & Infectious Disease, University of Cambridge, Cambridge, UK5 Cambridge COVID-19 Testing Centre and AstraZeneca, Anne Mclaren Building, Cambridge, UK6 NHS Blood and Transplant, Cambridge, UK7 Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK*Joint first authorship¶Joint last authorshipCorrespondence: [email protected] UK has initiated mass COVID-19 immunisation, with healthcare workers (HCWs) given early priority because of the potential for workplace exposure and risk of onward transmission to patients. The UK’s Joint Committee on Vaccination and Immunisation has recommended maximising the number of people vaccinated with first doses at the expense of early booster vaccinations, based on single dose efficacy against symptomatic COVID-19 disease.1-3At the time of writing, three COVID-19 vaccines have been granted emergency use authorisation in the UK, including the BNT162b2 mRNA COVID-19 vaccine (Pfizer-BioNTech). A vital outstanding question is whether this vaccine prevents or promotes asymptomatic SARS-CoV-2 infection, rather than symptomatic COVID-19 disease, because sub-clinical infection following vaccination could continue to drive transmission. This is especially important because many UK HCWs have received this vaccine, and nosocomial COVID-19 infection has been a persistent problem.Through the implementation of a 24 h-turnaround PCR-based comprehensive HCW screening programme at Cambridge University Hospitals NHS Foundation Trust (CUHNFT), we previously demonstrated the frequent presence of pauci- and asymptomatic infection amongst HCWs during the UK’s first wave of the COVID-19 pandemic.4 Here, we evaluate the effect of first-dose BNT162b2 vaccination on test positivity rates and cycle threshold (Ct) values in the asymptomatic arm of our programme, which now offers weekly screening to all staff.Vaccination of HCWs at CUHNFT began on 8th December 2020, with mass vaccination from 8th January 2021. Here, we analyse data from the two weeks spanning 18thto 31st January 2021, during which: (a) the prevalence of COVID-19 amongst HCWs remained approximately constant; and (b) we screened comparable numbers of vaccinated and unvaccinated HCWs. Over this period, 4,408 (week 1) and 4,411 (week 2) PCR tests were performed from individuals reporting well to work. We stratified HCWs <12 days or > 12 days post-vaccination because this was the point at which protection against symptomatic infection began to appear in phase III clinical trial.226/3,252 (0·80%) tests from unvaccinated HCWs were positive (Ct<36), compared to 13/3,535 (0·37%) from HCWs <12 days post-vaccination and 4/1,989 (0·20%) tests from HCWs ≥12 days post-vaccination (p=0·023 and p=0·004, respectively; Fisher’s exact test, Figure). This suggests a four-fold decrease in the risk of asymptomatic SARS-CoV-2 infection amongst HCWs ≥12 days post-vaccination, compared to unvaccinated HCWs, with an intermediate effect amongst HCWs <12 days post-vaccination.A marked reduction in infections was also seen when analyses were repeated with: (a) inclusion of HCWs testing positive through both the symptomatic and asymptomatic arms of the programme (56/3,282 (1·71%) unvaccinated vs 8/1,997 (0·40%) ≥12 days post-vaccination, 4·3-fold reduction, p=0·00001); (b) inclusion of PCR tests which were positive at the limit of detection (Ct>36, 42/3,268 (1·29%) vs 15/2,000 (0·75%), 1·7-fold reduction, p=0·075); and (c) extension of the period of analysis to include six weeks from December 28th to February 7th 2021 (113/14,083 (0·80%) vs 5/4,872 (0·10%), 7·8-fold reduction, p=1x10-9). In addition, the median Ct value of positive tests showed a non-significant trend towards increase between unvaccinated HCWs and HCWs > 12 days post-vaccination (23·3 to 30·3, Figure), suggesting that samples from vaccinated individuals had lower viral loads.We therefore provide real-world evidence for a high level of protection against asymptomatic SARS-CoV-2 infection after a single dose of BNT162b2 vaccine, at a time of predominant transmission of the UK COVID-19 variant of concern 202012/01 (lineage B.1.1.7), and amongst a population with a relatively low frequency of prior infection (7.2% antibody positive).5This work was funded by a Wellcome Senior Clinical Research Fellowship to MPW (108070/Z/15/Z), a Wellcome Principal Research Fellowship to PJL (210688/Z/18/Z), and an MRC Clinician Scientist Fellowship (MR/P008801/1) and NHSBT workpackage (WPA15-02) to NJM. Funding was also received from Addenbrooke’s Charitable Trust and the Cambridge Biomedical Research Centre. We also acknowledge contributions from all staff at CUHNFT Occupational Health and Wellbeing and the Cambridge COVID-19 Testing Centre.

Guangming Wang

and 4 more

Tam Hunt

and 1 more

Tam Hunt [1], Jonathan SchoolerUniversity of California Santa Barbara Synchronization, harmonization, vibrations, or simply resonance in its most general sense seems to have an integral relationship with consciousness itself. One of the possible “neural correlates of consciousness” in mammalian brains is a combination of gamma, beta and theta synchrony. More broadly, we see similar kinds of resonance patterns in living and non-living structures of many types. What clues can resonance provide about the nature of consciousness more generally? This paper provides an overview of resonating structures in the fields of neuroscience, biology and physics and attempts to coalesce these data into a solution to what we see as the “easy part” of the Hard Problem, which is generally known as the “combination problem” or the “binding problem.” The combination problem asks: how do micro-conscious entities combine into a higher-level macro-consciousness? The proposed solution in the context of mammalian consciousness suggests that a shared resonance is what allows different parts of the brain to achieve a phase transition in the speed and bandwidth of information flows between the constituent parts. This phase transition allows for richer varieties of consciousness to arise, with the character and content of that consciousness in each moment determined by the particular set of constituent neurons. We also offer more general insights into the ontology of consciousness and suggest that consciousness manifests as a relatively smooth continuum of increasing richness in all physical processes, distinguishing our view from emergentist materialism. We refer to this approach as a (general) resonance theory of consciousness and offer some responses to Chalmers’ questions about the different kinds of “combination problem.”  At the heart of the universe is a steady, insistent beat: the sound of cycles in sync…. [T]hese feats of synchrony occur spontaneously, almost as if nature has an eerie yearning for order. Steven Strogatz, Sync: How Order Emerges From Chaos in the Universe, Nature and Daily Life (2003) If you want to find the secrets of the universe, think in terms of energy, frequency and vibration.Nikola Tesla (1942) I.               Introduction Is there an “easy part” and a “hard part” to the Hard Problem of consciousness? In this paper, we suggest that there is. The harder part is arriving at a philosophical position with respect to the relationship of matter and mind. This paper is about the “easy part” of the Hard Problem but we address the “hard part” briefly in this introduction.  We have both arrived, after much deliberation, at the position of panpsychism or panexperientialism (all matter has at least some associated mind/experience and vice versa). This is the view that all things and processes have both mental and physical aspects. Matter and mind are two sides of the same coin.  Panpsychism is one of many possible approaches that addresses the “hard part” of the Hard Problem. We adopt this position for all the reasons various authors have listed (Chalmers 1996, Griffin 1997, Hunt 2011, Goff 2017). This first step is particularly powerful if we adopt the Whiteheadian version of panpsychism (Whitehead 1929).  Reaching a position on this fundamental question of how mind relates to matter must be based on a “weight of plausibility” approach, rather than on definitive evidence, because establishing definitive evidence with respect to the presence of mind/experience is difficult. We must generally rely on examining various “behavioral correlates of consciousness” in judging whether entities other than ourselves are conscious – even with respect to other humans—since the only consciousness we can know with certainty is our own. Positing that matter and mind are two sides of the same coin explains the problem of consciousness insofar as it avoids the problems of emergence because under this approach consciousness doesn’t emerge. Consciousness is, rather, always present, at some level, even in the simplest of processes, but it “complexifies” as matter complexifies, and vice versa. Consciousness starts very simple and becomes more complex and rich under the right conditions, which in our proposed framework rely on resonance mechanisms. Matter and mind are two sides of the coin. Neither is primary; they are coequal.  We acknowledge the challenges of adopting this perspective, but encourage readers to consider the many compelling reasons to consider it that are reviewed elsewhere (Chalmers 1996, Griffin 1998, Hunt 2011, Goff 2017, Schooler, Schooler, & Hunt, 2011; Schooler, 2015).  Taking a position on the overarching ontology is the first step in addressing the Hard Problem. But this leads to the related questions: at what level of organization does consciousness reside in any particular process? Is a rock conscious? A chair? An ant? A bacterium? Or are only the smaller constituents, such as atoms or molecules, of these entities conscious? And if there is some degree of consciousness even in atoms and molecules, as panpsychism suggests (albeit of a very rudimentary nature, an important point to remember), how do these micro-conscious entities combine into the higher-level and obvious consciousness we witness in entities like humans and other mammals?  This set of questions is known as the “combination problem,” another now-classic problem in the philosophy of mind, and is what we describe here as the “easy part” of the Hard Problem. Our characterization of this part of the problem as “easy”[2] is, of course, more than a little tongue in cheek. The authors have discussed frequently with each other what part of the Hard Problem should be labeled the easier part and which the harder part. Regardless of the labels we choose, however, this paper focuses on our suggested solution to the combination problem.  Various solutions to the combination problem have been proposed but none have gained widespread acceptance. This paper further elaborates a proposed solution to the combination problem that we first described in Hunt 2011 and Schooler, Hunt, and Schooler 2011. The proposed solution rests on the idea of resonance, a shared vibratory frequency, which can also be called synchrony or field coherence. We will generally use resonance and “sync,” short for synchrony, interchangeably in this paper. We describe the approach as a general resonance theory of consciousness or just “general resonance theory” (GRT). GRT is a field theory of consciousness wherein the various specific fields associated with matter and energy are the seat of conscious awareness.  A summary of our approach appears in Appendix 1.  All things in our universe are constantly in motion, in process. Even objects that appear to be stationary are in fact vibrating, oscillating, resonating, at specific frequencies. So all things are actually processes. Resonance is a specific type of motion, characterized by synchronized oscillation between two states.  An interesting phenomenon occurs when different vibrating processes come into proximity: they will often start vibrating together at the same frequency. They “sync up,” sometimes in ways that can seem mysterious, and allow for richer and faster information and energy flows (Figure 1 offers a schematic). Examining this phenomenon leads to potentially deep insights about the nature of consciousness in both the human/mammalian context but also at a deeper ontological level.

Susanne Schilling*^

and 9 more

Jessica mead

and 6 more

The construct of wellbeing has been criticised as a neoliberal construction of western individualism that ignores wider systemic issues including increasing burden of chronic disease, widening inequality, concerns over environmental degradation and anthropogenic climate change. While these criticisms overlook recent developments, there remains a need for biopsychosocial models that extend theoretical grounding beyond individual wellbeing, incorporating overlapping contextual issues relating to community and environment. Our first GENIAL model \cite{Kemp_2017} provided a more expansive view of pathways to longevity in the context of individual health and wellbeing, emphasising bidirectional links to positive social ties and the impact of sociocultural factors. In this paper, we build on these ideas and propose GENIAL 2.0, focusing on intersecting individual-community-environmental contributions to health and wellbeing, and laying an evidence-based, theoretical framework on which future research and innovative therapeutic innovations could be based. We suggest that our transdisciplinary model of wellbeing - focusing on individual, community and environmental contributions to personal wellbeing - will help to move the research field forward. In reconceptualising wellbeing, GENIAL 2.0 bridges the gap between psychological science and population health health systems, and presents opportunities for enhancing the health and wellbeing of people living with chronic conditions. Implications for future generations including the very survival of our species are discussed.  

Mark Ferris

and 14 more

IntroductionConsistent with World Health Organization (WHO) advice [1], UK Infection Protection Control guidance recommends that healthcare workers (HCWs) caring for patients with coronavirus disease 2019 (COVID-19) should use fluid resistant surgical masks type IIR (FRSMs) as respiratory protective equipment (RPE), unless aerosol generating procedures (AGPs) are being undertaken or are likely, when a filtering face piece 3 (FFP3) respirator should be used [2]. In a recent update, an FFP3 respirator is recommended if “an unacceptable risk of transmission remains following rigorous application of the hierarchy of control” [3]. Conversely, guidance from the Centers for Disease Control and Prevention (CDC) recommends that HCWs caring for patients with COVID-19 should use an N95 or higher level respirator [4]. WHO guidance suggests that a respirator, such as FFP3, may be used for HCWs in the absence of AGPs if availability or cost is not an issue [1].A recent systematic review undertaken for PHE concluded that: “patients with SARS-CoV-2 infection who are breathing, talking or coughing generate both respiratory droplets and aerosols, but FRSM (and where required, eye protection) are considered to provide adequate staff protection” [5]. Nevertheless, FFP3 respirators are more effective in preventing aerosol transmission than FRSMs, and observational data suggests that they may improve protection for HCWs [6]. It has therefore been suggested that respirators should be considered as a means of affording the best available protection [7], and some organisations have decided to provide FFP3 (or equivalent) respirators to HCWs caring for COVID-19 patients, despite a lack of mandate from local or national guidelines [8].Data from the HCW testing programme at Cambridge University Hospitals NHS Foundation Trust (CUHNFT) during the first wave of the UK severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic indicated a higher incidence of infection amongst HCWs caring for patients with COVID-19, compared with those who did not [9]. Subsequent studies have confirmed this observation [10, 11]. This disparity persisted at CUHNFT in December 2020, despite control measures consistent with PHE guidance and audits indicating good compliance. The CUHNFT infection control committee therefore implemented a change of RPE for staff on “red” (COVID-19) wards from FRSMs to FFP3 respirators. In this study, we analyse the incidence of SARS-CoV-2 infection in HCWs before and after this transition.

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Yu Fukasawa

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1. Activities of wood decomposer fungi alter abiotic and biotic properties of deadwood, which are important for tree seedling regeneration on nurse logs. However, the effects were seldom evaluated experimentally. 2. In this study, we examined germination, growth, and survival of six arbuscular mycorrhizal and six ectomycorrhizal tree species on three substrates (brown rot logs, white rot logs, and soil) by seed sowing experiments in a mixed forest dominated by Pinus densiflora and Quercus serrata. We also analyzed fungal communities in these substrates by rDNA ITS1 sequencing. 3. Some significant substrate effects were found on seedling performance when comparing wood decay types, but these were not clearly consistent across mycorrhizal status of the seedlings. Nevertheless, seedlings of arbuscular mycorrhizal trees tended to show better growth on brown rot logs than on white rot logs, whereas ectomycorrhizal tree seedlings tended to survive better on white rot logs and soil compared to brown rot logs. 4. The fungal community was significantly different across three substrates. Richness of Operational Taxonomic Units (OTUs) of arbuscular mycorrhizal fungi was largest in brown rot logs, whereas OTU richness of ectomycorrhizal fungi was largest in soil. 5. Synthesis: The effects of fungal wood decay type on nurse log regeneration of tree seedlings might be partly attributable to water content and fungal communities in the logs. Particularly, rich communities of arbuscular mycorrhizal fungi in brown rot logs could assist in the growth of arbuscular mycorrhizal tree seedlings.

Christian Mazimpaka

and 6 more

Background: The Patient Voice Program and Citizen Voice and Action models use scorecard meetings for community-provider-government dialogue to improve health services. This study evaluates the responsiveness of leaders and providers to concerns voiced by citizens through these scorecard meetings at the health center and district office levels in Rwanda. Methods: We conducted a cross-sectional study from July to September 2022 in 325 Rwandan health centers across 20 districts. Responsiveness was measured by comparing resolved issues to raised issues. Logistic regression identified predictors of issue resolution, with a p-value less than 0.05 considered significant. Median responsiveness turnaround time was also analyzed. Results: In total, 59.4% (1,163) of the identified gaps were resolved. Facility-level issues experienced a higher resolution rate (65.9%) than district-level issues (35.4%). Gaps at the facility level were 3.24 times more likely to be resolved than those at the district level (OR: 3.24, p<0.001, 95% CI: [2.48,4.25]). Integrated gaps had 1.46 times higher odds of resolution compared to issues stemming from reproductive, maternal, newborn, and child health services (OR: 1.46, p<0.05, 95% CI: [1.13,1.88]). The median responsiveness turnaround time for resolving a gap was approximately 15.4 months (IQR: 6.7-25.8). Conclusions: The study shows that Patient Voice Program and Citizen Voice and Action models are effective in addressing healthcare service gaps. By promoting collaboration among communities, healthcare providers, and governments, these models facilitate targeted, locally-supported solutions that significantly improve the resolution of health service delivery issues.

Fabio Squarcio

and 2 more

Converging electrophysiological, molecular, and ultrastructural evidence supports the hypothesis that sleep promotes a net decrease in excitatory synaptic strength, counteracting the net synaptic potentiation caused by ongoing learning during waking. However, several outstanding questions about sleep-dependent synaptic weakening remain. Here, we address some of these questions by using two established molecular markers of synaptic strength, the levels of the calcium-permeable AMPA (Alpha-Amino-3-Hydroxy-5-Methyl-4-Isoxazole Propionic Acid) receptors containing the GluA1 subunit, and the phosphorylation of GluA1 at serine 845. We previously found that, in the rat cortex and hippocampus, these markers are lower after 6-8 hours of sleep than after the same time spent awake. Here, we measure GluA1 expression in mouse cortex after 5 hours of either sleep, sleep deprivation, recovery sleep after sleep deprivation, or selective REM sleep deprivation (32 C57BL/B6 adult mice, 16 females). We find that relative to after sleep deprivation, synaptic GluA1 expression is lower after sleep independent of whether the mice were allowed to enter REM sleep. Moreover, 5 hours of recovery sleep following acute sleep deprivation are enough to renormalize GluA1 expression. In a pilot study in old mice (12 C57BL/B6 male mice, 20-month-old) we also find that GluA1 expression is high after sleep deprivation and low after sleep and recovery sleep. Thus, the renormalization of GluA1 expression crucially relies on NREM sleep and can occur in a few hours of sleep after acute sleep deprivation. Moreover, as measured by GluA1 expression, it appears that sleep-dependent synaptic weakening is unaffected by aging.

Jie Zheng

and 5 more

Rabia Iqbal

and 7 more

Background: Multiple myeloma (MM) has different complications, including renal failure, anemia, infections, metabolic complications, and skeletal problems. Hypercalcemia is the most common metabolic complication, and the presence of hypercalcemia indicates worse outcomes. Aims: The study aims to examine outcomes such as hospitalization costs, length of stay, survival rates, and the incidence of complications of hypercalcemia in multiple myeloma patients admitted in the United States from 2017 to 2020. Methods: We performed a retrospective analysis using the National Inpatient Sample database to determine the incidence of hypercalcemia in patients admitted to United States hospitals from 2017 to 2020. Univariate and multivariate logistic regression were used to calculate the odds ratio. We used STATA software 17 to perform the analysis. Results: We found that the total number of patients with MM was 437799, out of which 8.6% had hypercalcemia. The mean age of the patients was 69 years, and hypercalcemia was found to be more common in males (55%) than females (45%). The presence of hypercalcemia was also associated with increased mortality (adjusted odds ratio 1.3, p-value 0.00). It was also seen that MM patients who had hypercalcemia had a higher risk of complications, including acute kidney injury (OR 3, p<0.05), hyperkalemia (OR 1.8, p-value <0.05), metabolic acidosis (1.4, p-value <0.05), spinal cord compression (OR 0.9, p-value >0.05), increased length of stay (OR 3, p-value <0.05), and higher cost of hospitalizations (p-value <0.05). Conclusion: The data is also limited to the demographic characteristics, impact, and outcomes of hypercalcemia on patients with MM. This study contributes valuable insights into the clinical implications of hypercalcemia in patients with multiple myeloma (MM). It fills existing gaps in the literature by utilizing a large population-based dataset.

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Mohammad Rowshan

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Channel coding plays a pivotal role in ensuring reliable communication over wireless channels. With the growing need for ultra-reliable communication in emerging wireless use cases, the significance of channel coding has amplified. Furthermore, minimizing decoding latency is crucial for critical-mission applications, while optimizing energy efficiency is paramount for mobile and the Internet of Things (IoT) communications. As the fifth generation (5G) of mobile communications is currently in operation and 5G-advanced is on the horizon, the objective of this paper is to assess prominent channel coding schemes in the context of recent advancements and the anticipated requirements for the sixth generation (6G). In this paper, after considering the potential impact of channel coding on key performance indicators (KPIs) of wireless networks, we review the evolution of mobile communication standards and the organizations involved in the standardization, from the first generation (1G) to the current 5G, highlighting the technologies integral to achieving targeted KPIs such as reliability, data rate, latency, energy efficiency, spectral efficiency, connection density, and traffic capacity. Following this, we delve into the anticipated requirements for potential use cases in 6G. The subsequent sections of the paper focus on a comprehensive review of three primary coding schemes utilized in past generations and their recent advancements: lowdensity parity-check (LDPC) codes, turbo codes (including convolutional codes), and polar codes (alongside Reed-Muller codes). Additionally, we examine alternative coding schemes like Fountain codes (also known as rate-less codes), sparse regression codes, among others. Our evaluation includes a comparative analysis of error correction performance and the performance of hardware implementation for these coding schemes, providing insights into their potential and suitability for the upcoming 6G era. Lastly, we will briefly explore considerations such as higher-order modulations and waveform design, examining their contributions to enhancing key performance indicators in conjunction with channel coding schemes.
The involvement of users in the product development process can significantly enhance product quality. The relationship between user experience and knowledge in product design contributes to product efficiency during the development phase. Users often struggle to align their perceptions, leading to extended product usage times and an inability to react to potential performance variations. Product manufacturers also face challenges in identifying suitable features that can positively impact product success and marketability. User experience in product interactions, encompassing both aesthetic and functional aspects, plays a pivotal role in influencing user evaluations and distinguishing characteristics crucial for achieving product success. Determining user knowledge’s influence on product success characteristics can provide valuable insights for the new product development process. This study conducted a survey to gather user experiences and knowledge, aiming to enhance the understanding of how users perceive products. This understanding is crucial for identifying product success characteristics, encompassing aspects such as specifications, sustainability, and recognition, which are instrumental in achieving overall product success. The results of the survey indicate that user knowledge, emotional experiences, and product attribute knowledge can assist product designers and manufacturers in identifying key characteristics for success during the early stages of the new product development process.

Karma Norbu

and 3 more

Introduction: Scrub typhus is a neglected life threatening acute febrile illness caused by bacteria Orientia tsutsugamushi and it is a vector-borne zoonotic disease. In 2009, scrub typhus outbreak at Gedu has awakened Bhutan on the awareness and testing of the disease.Information and data of the study highlights the need for in depth surveillance, awareness among prescribers and initiate preventive measures in the country. Methods: We used retrospective descriptive study through review of laboratory registers across three health centres in Zhemgang district, south central Bhutan. The laboratories registers have been transcribed into CSV file using Microsoft excel. Variables of interest were collected from the registers and then analysed using open statistical software R, (R Core Team (2020). R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria.) And use of mStats package, (MyoMinnOo (2020). mStats: Epidemiological DataAnalysis. R package version 3.4.0.) Results: Of the total 922 tests prescribed for suspected scrub typhus in the three health centers in Zhemgang, only 8.2 % (n=76) were tested positive. Of these, Panbang Hospital had highest reported positive for scrub typhus with 56.6 %( n=43) followed by Yebilaptsa Hospital 35.5 %( n=27) and Zhemgang Hospital with 7.9 %( n=6). The female gender is comparably more affected as opposed to male with 57.9% (n=44) of the positive cases being female. The prevalence of scrub typhus seems to be affected by the seasonal variation as the months of Spring, Summer and Autumn together accounts for 98.7%(n=75) of total positive cases. The year 2019 noted significant scrub typhus cases accounting to 89.5 %(n=68) of the total positive cases over the two years. Conclusions:The overall tests tested positive of the scrub typhus infection within two years was 8.2%.

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