Effect of mild COVID-19 on health-related quality of life.

Background: Little is known about the effects of a mild SARS-CoV-2 infection on health-related quality of life. Methods: This prospective observational study of symptomatic adults (18-87 years) who sought outpatient care for an acute respiratory illness, was conducted from 3/30/2020 to 4/30/2021. Participants completed the Short Form Health Survey (SF-12) at enrollment and 6-8 weeks later, to report their physical and mental health function levels as measured by the physical health and mental health composite scores (PHC and MHC, respectively). PHC and MHC scores for COVID-19 cases and non-COVID cases were compared using t-tests. Multivariable regression modeling was used to determine predictors of physical and mental health function at follow-up. Results: Of 2301 enrollees, 426 COVID-19 cases and 547 non-COVID cases completed both surveys. PHC improved significantly from enrollment to follow-up for both COVID-19 cases (5.4 ± 0.41; P < 0.001) and non-COVID cases (3.3 ± 0.32; P < 0.001); whereas MHC improved significantly for COVID-19 cases (1.4 ± 0.51; P < 0.001) and decreased significantly for non-COVID cases (-0.8 ± 0.37; P < 0.05). Adjusting for enrollment PHC, the most important predictors of PHC at follow-up included male sex (ß = 1.17; SE = 0.5; P = 0.021), having COVID-19 (ß = 1.99; SE = 0.54; P < 0.001); and non-white race (ß = -2.01; SE = 0.70; P = 0.004). Adjusting for enrollment MHC, the most important predictors of MHC at follow-up included male sex (ß = 1.92; SE = 0.63; P = 0.002) and having COVID-19 (ß = 2.42; SE = 0.67; P < 0.001). Conclusion: Both COVID-19 cases and non-COVID cases reported improved physical health function at 6-8 weeks' convalescence; whereas mental health function improved among COVID-19 cases but declined among non-COVID cases. Both physical and mental health functioning were significantly better among males with COVID-19 than females.

Impact of Integrating Rabies Education Into the Curriculum of Public Elementary Schools in Ilocos Norte, Philippines on Rabies Knowledge, and Animal Bite Incidence.

As part of a province wide rabies elimination program, rabies specific information was integrated into the curriculum of all public elementary schools in Ilocos Norte, Philippines using a specifically developed teachers' manual. The rabies educational messages included rabies, animal bite prevention, bite management and responsible pet ownership and were integrated into lessons in several subjects. Four elementary schools were randomly selected and an assessment of the change in student's rabies knowledge and animal bite incidence were conducted. The study tested all students in grades 1-5 before the curriculum integration was implemented and retested these cohorts 1 year later, after implementation. Awareness of rabies was high before the implementation, likely due to the province-wide elimination campaign. However, awareness still increased significantly across all schools, and detailed knowledge of rabies increased significantly in all but one school and age cohort. Bite incidence in the 6 months prior to each survey was also recorded and the percentage of students suffering animal bites fell significantly between the two tests. The data suggested that knowledge increase correlated with decreased bite incidence in some groups but not all, suggesting a more complex relationship between knowledge acquisition and behavioral change which warrants further investigation.

The evaluation of Animal Bite Treatment Centers in the Philippines from a patient perspective.

BACKGROUND: The Philippines has built an extensive decentralised network of Animal Bite Treatment Centers (ABTCs) to help bite victims receive timely rabies post-exposure prophylaxis (PEP) at little cost. This study surveyed patients in the community and at ABTCs of three provinces to assess animal bite/scratch incidence, health-seeking behaviour and PEP-related out-of pocket expenses (OOPE). METHODOLOGY AND PRINCIPAL FINDINGS: During community surveys in 90 barangays (neighbourhoods), 53% of households reported at least one animal bite /scratch injury over the past 3 years, similar across urban and rural barangays. Overall bite/scratch incidences in 2016-17 were 67.3, 41.9 and 48.8 per 1,000 population per year for Nueva Vizcaya, Palawan and Tarlac respectively. Incidences were around 50% higher amongst those under 15 years of age, compared to -those older than 15. Household awareness of the nearest ABTCs was generally over 80%, but only 44.9% sought proper medical treatment and traditional remedies were still frequently used. The proportion of patients seeking PEP was not related to the distance or travel time to the nearest ABTC. For those that did not seek medical treatment, most cited a lack of awareness or insufficient funds and almost a third visited a traditional healer. No deaths from bite/scratch injuries were reported. A cohort of 1,105 patients were interviewed at six ABTCs in early 2017. OOPE varied across the ABTCs, from 5.53 USD to 37.83 USD per patient, primarily dependent on the need to pay for immunization if government supplies had run out. Overall, 78% of patients completed the recommended course, and the main reason for non-completion was a lack of time, followed by insufficient funds. Dog observation data revealed that 85% of patients were not truly exposed to rabies, and education in bite prevention might reduce provoked bites and demand for PEP. An accompanying paper details the ABTC network from the health provider's perspective.

The evaluation of operating Animal Bite Treatment Centers in the Philippines from a health provider perspective.

BACKGROUND: The Philippine government has an extensive network of 513 Animal Bite Treatment Centers (ABTCs) to supply rabies post exposure prophylaxis (PEP), reaching over 1 million bite victims in 2016. The network was evaluated using a review of existing national and provincial data, key informant interviews and surveys in sample ABTCs to determine the cost-effectiveness of this network in preventing human rabies deaths. METHODOLOGY AND PRINCIPAL FINDINGS: One urban and one rural ABTC in each of three selected provinces were studied in more detail. PEP delivery generally followed national guidance based on best practices, but there was evidence of operational challenges in supplying all ABTCs with adequate biologics and recently trained staff. Funding was contributed by different levels of government and in some clinics, patients paid for a significant fraction of the total cost. From a health provider perspective including both fixed and variable costs, the average PEP course delivered cost USD 32.91 /patient across urban ABTCs (with higher patient throughput) and USD 57.21 /patient across rural ABTCs. These costs suggests that PEP provision in the Philippines cost USD 37.6 million in 2016, with a cost per life saved of USD 8,290. An analysis of the 2,239 suspected rabies deaths from 2008 to 2016 showed no significant decline, and from 2014-16 an average of 8,534 years of life were lost annually. The incidence of rabies deaths from 2014-16 was not clearly related to the provision of ABTCs (per 100,000 population) or human population density, but deaths were more common in higher income provinces. CONCLUSIONS/SIGNIFICANCE: In the context of comprehensive rabies control (including dog vaccination and public awareness) ways to reduce this high expenditure on PEP should be explored, to most cost-effectively reach the elimination of human rabies deaths. This paper is accompanied by another containing data on the operation of ABTCs network from a patient perspective.

The Role of Dog Population Management in Rabies Elimination-A Review of Current Approaches and Future Opportunities.

Free-roaming dogs and rabies transmission are integrally linked across many low-income countries, and large unmanaged dog populations can be daunting to rabies control program planners. Dog population management (DPM) is a multifaceted concept that aims to improve the health and well-being of free-roaming dogs, reduce problems they may cause, and may also aim to reduce dog population size. In theory, DPM can facilitate more effective rabies control. Community engagement focused on promoting responsible dog ownership and better veterinary care could improve the health of individual animals and dog vaccination coverage, thus reducing rabies transmission. Humane DPM tools, such as sterilization, could theoretically reduce dog population turnover and size, allowing rabies vaccination coverage to be maintained more easily. However, it is important to understand local dog populations and community attitudes toward them in order to determine whether and how DPM might contribute to rabies control and which DPM tools would be most successful. In practice, there is very limited evidence of DPM tools achieving reductions in the size or turnover of dog populations in canine rabies-endemic areas. Different DPM tools are frequently used together and combined with rabies vaccinations, but full impact assessments of DPM programs are not usually available, and therefore, evaluation of tools is difficult. Surgical sterilization is the most frequently documented tool and has successfully reduced dog population size and turnover in a few low-income settings. However, DPM programs are mostly conducted in urban settings and are usually not government funded, raising concerns about their applicability in rural settings and sustainability over time. Technical demands, costs, and the time necessary to achieve population-level impacts are major barriers. Given their potential value, we urgently need more evidence of the effectiveness of DPM tools in the context of canine rabies control. Cheaper, less labor-intensive tools for dog sterilization will be extremely valuable in realizing the potential benefits of reduced population turnover and size. No one DPM tool will fit all situations, but if DPM objectives are achieved dog populations may be stabilized or even reduced, facilitating higher dog vaccination coverages that will benefit rabies elimination efforts.

The Road to Dog Rabies Control and Elimination-What Keeps Us from Moving Faster?

Rabies, a vaccine preventable neglected tropical disease, still claims an estimated 35,000-60,000 human lives annually. The international community, with more than 100 endemic countries, has set a global target of 0 human deaths from dog-transmitted rabies by 2030. While it has been proven in several countries and regions that elimination of rabies as a public health problem is feasible and tools are available, rabies deaths globally have not yet been prevented effectively. While there has been extensive rabies research, specific areas of implementation for control and elimination have not been sufficiently addressed. This article highlights some of the commonest perceived barriers for countries to implementing rabies control and elimination programs and discusses possible solutions for sociopolitical, organizational, technical, and resource-linked requirements, following the pillars of the global framework for the elimination of dog-mediated human rabies adopted at the global rabies meeting in December 2015.

The Ilocos Norte Communities against Rabies Exposure Elimination Project in the Philippines: Epidemiological and Economic Aspects.

As canine rabies control in Africa and Asia transitions from research-led proof-of-concept studies to government-led programs for elimination, experience and evidence of their impact and costs must be shared for the benefit of future programs. The Ilocos Norte Communities against Rabies Exposure project was implemented in April 2012 by the provincial veterinary and health offices and supported by many other partners. It delivered a comprehensive dog vaccination program and increased awareness of the need for postexposure prophylaxis (PEP), aiming to eliminate human and animal rabies cases from Ilocos Norte by 2015. Prior to the intervention, confirmed rabies cases in dogs were between 19 and 50 per year (2008-2011). The primary outcome of the project was a reduction in rabies cases in both dogs and humans to 0 in 2014 and 2015, which has subsequently been maintained. Animal bite consultations increased significantly during the project. Economic data for the dog vaccination and PEP components of the project were collated for two sites: Laoag City (an urban setting) and Dingras Municipality (a rural setting) between 2012 and 2014. The average programmatic cost of vaccinating each dog was $4.54 in Laoag City and $8.65 in Dingras, and costs fell as the project reached more dogs. The average costs of providing PEP were $69.72 per patient and $49.02 per patient for the two sites, respectively, again falling as the project reached more people. External donor contributions contributed less than 20% of dog vaccination costs and less than 1% of PEP costs. The project demonstrated that rabies elimination can be achieved in a short period of time, with concerted effort across multiple sectors. A lack of clear dog population estimates hampered interpretation of some aspects of the programme. From 2016, the provincial government has assumed complete responsibility for the programme and must now continue the vaccination and surveillance efforts. Although safeguards are in place, reintroduction from surrounding areas remains a threat, and vigilance must be maintained.

Difficulties in estimating the human burden of canine rabies.

Current passive surveillance data for canine rabies, particularly for the regions where the burden is highest, are inadequate for appropriate decision making on control efforts. Poor enforcement of existing legislation and poor implementation of international guidance reduce the effectiveness of surveillance systems, but another set of problems relates to the fact that canine rabies is an untreatable condition which affects very poor sectors of society. This results in an unknown, but potentially large proportion of rabies victims dying outside the health system, deaths that are unlikely to be recorded by surveillance systems based on health center records. This article critically evaluates the potential sources of information on the number of human deaths attributable to canine rabies, and how we might improve the estimates required to move towards the goal of global canine rabies elimination.

Global partnerships are critical to advance the control of Neglected Zoonotic Diseases: The case of the Global Alliance for Rabies Control.

There is a need for innovation to improve control of all Neglected Zoonotic Diseases (NZDs). The Global Alliance for Rabies Control was formed to prevent human deaths from rabies and relieve the burden of rabies in other animal populations, especially dogs. It aims to identify reasons for the neglect of rabies in developing countries and to develop strategies to improve rabies control. Through initiatives such as World Rabies Day and the Partners for Rabies Prevention, progress has been made towards increased awareness of the burden of rabies transmitted by dogs at scales from local to international. An evidence base of the feasibility of canine rabies elimination has been built up and now easier access to information and tools enables countries to design and implement rabies elimination strategies in a logical way, utilizing the structures of regional networks for rabies control. The body of evidence has built consensus amongst international stakeholders in rabies control and is now being used to encourage international policy change, attract investment and increase delivery of effective rabies control programmes in canine rabies endemic countries.

Cross-sectional study of the prehospital management of adult patients with a suspected seizure (EPIC1).

OBJECTIVES: Suspected seizures are a common reason for emergency calls to ambulance services. Prehospital management of these patients is an important element of good quality care. The aim of this study, conducted in a regional ambulance service in the UK, was to quantify the number of emergency telephone calls for suspected seizures in adults, the associated costs, and to describe the patients' characteristics, their prehospital management and their immediate outcomes. DESIGN: Quantitative cross-sectional study using routinely collected data and a detailed review of the clinical records of a consecutive series of adult patients (≥ 16 years). SETTING: A regional ambulance service within the National Health Service in England. PARTICIPANTS: Cross-sectional data from all 605,481 adult emergency incidents managed by the ambulance service from 1 April 2012 to 31 March 2013. We selected a consecutive series of 178 individual incidents from May 2012 for more detailed analysis (132 after exclusions and removal of non-seizure cases). RESULTS: Suspected seizures made up 3.3% of all emergency incidents. True medical emergencies were uncommon but 3.3% had partially occluded airways, 6.8% had ongoing seizure activity and 59.1% had clinical problems in addition to the seizure (29.1% involving injury). Emergency vehicles were dispatched for 97.2% of suspected seizures, the seizure had terminated on arrival in 93.2% of incidents, 75% of these patients were transported to hospital. The estimated emergency management cost per annum of suspected seizures in the English ambulance services is £45.2 million (€64.0 million, $68.6 million). CONCLUSIONS: Many patients with suspected seizures could potentially be treated more effectively and at lower cost by modifying ambulance call handling protocols. The development of innovative care pathways could give call handlers and paramedics alternatives to hospital transportation. Increased adoption of care plans could reduce 999 calls and could increase the rates of successful home or community treatment.

World Rabies Day - a decade of raising awareness.

World Rabies Day was set up in 2007 to raise global awareness about rabies, to provide information on how to prevent the disease in at-risk communities and support advocacy for increased efforts in rabies control. It is held annually on September 28th, with events, media outreach and other initiatives carried out by individuals, professionals, organisations and governments from the local to the international level. The Global Alliance for Rabies Control coordinates World Rabies Day, amplifying the campaign's reach through the provision of a central event platform and resources to support events across the world, the promotion of messages through key rabies stakeholders, and the implementation of specific activities to highlight particular issues. Over the last decade, more than 1,700 registered events have been held across the world and shared with others in the global rabies community. Events in canine rabies endemic countries, particularly in Africa and Asia, have increased over time. Beyond the individual events, World Rabies Day has gained the support of governments and international agencies that recognise its value in supporting existing rabies control initiatives and advocating for improvements. As the rabies landscape has changed, World Rabies Day remains a general day of awareness but has also become an integral part of national, regional and global rabies elimination strategies. The global adoption of 2030 as the goal for the elimination of rabies as a public health threat has led to even greater opportunities for World Rabies Day to make a sustainable impact on rabies, by bringing the attention of policy makers and donors to the ongoing situation and elimination efforts in rabies-endemic countries.

Global epidemiology of canine rabies: past, present, and future prospects.

The rabies virus, a public health scourge from ancient times, is currently responsible for an estimated 59,000 human deaths a year, almost all transmitted via dog bites. It causes considerable economic impacts on developing countries, primarily in Africa and Asia, which can least afford these losses. However, despite its almost 100% case fatality rate, canine rabies is a completely preventable disease, and historic examples of canine rabies elimination in the developed world attest to this. Over the last decade, programs based on eliminating the source of the disease from dogs have shown success in reducing the public health burden of canine rabies in developing countries, notably across Latin America, and this has contributed to the growing evidence base necessary to change attitudes toward the feasibility of global canine rabies elimination. More recently, assessments of the current economic burden of canine rabies and the potential cost savings achievable through mass dog vaccinations have been added to this evidence base. Tools and support are available from the international community to help countries move progressively toward canine rabies elimination, and there is optimism that global freedom from canine rabies can be achieved within the next few decades.

Competitive suppression in mixed-clone parasite cultures.

Mixed-genotype infections occur frequently in natural populations. Parasite genotypes are expected to interact within a host: competing for shared nutrients and being affected by the host's immune response to each other. Theoretically, competing parasites can be expected to exhibit increased rates of replication. Here, we investigate whether interactions between clones of Theileria annulata, a protozoan parasite of cattle, affect clones' replication rates in mixed cultures in vitro. Intrinsic replication rates and carrying capacities estimated from single-clone control cultures were used to predict replication rates of mixed cultures under different competitive assumptions. Mixed-culture dynamics deviated significantly from expectations in five out of six different clone combinations tested. Contrary to expectation, mixed cultures often replicated more slowly than predicted from single-clone control cultures. Competition coefficients were calculated from the mixed-culture data and a competitive hierarchy of clones determined. The results suggest that inherent competitive ability may be greater in clones with lower carrying capacities-those clones which would otherwise be excluded in a genetically diverse environment. Moreover, significant negative deviations from expected replication rates corresponded with successful out-competing of a higher carrying capacity clone by a lower carrying capacity clone.

Identifying reservoirs of infection: a conceptual and practical challenge.

Many infectious agents, especially those that cause emerging diseases, infect more than one host species. Managing reservoirs of multihost pathogens often plays a crucial role in effective disease control. However, reservoirs remain variously and loosely defined. We propose that reservoirs can only be understood with reference to defined target populations. Therefore, we define a reservoir as one or more epidemiologically connected populations or environments in which the pathogen can be permanently maintained and from which infection is transmitted to the defined target population. Existence of a reservoir is confirmed when infection within the target population cannot be sustained after all transmission between target and nontarget populations has been eliminated. When disease can be controlled solely by interventions within target populations, little knowledge of potentially complex reservoir infection dynamics is necessary for effective control. We discuss the practical value of different approaches that may be used to identify reservoirs in the field.

Theileria annulata: virulence and transmission from single and mixed clone infections in cattle.

Theoretically, parasite virulence should be higher for faster growing parasites, and higher in mixed infections compared to single-clone infections. Virulence should also be positively correlated to transmission rates. Theileria annulata provides a good model system for studying such hypotheses, as parasite replication causes harm to the host, and there is evidence suggesting that the genetic complexity of an infection might affect its virulence. Two clones of T. annulata were chosen, one fast growing and one slow growing in vitro and these were used to establish cattle infections, either alone, or in a mixed infection. Virulence was measured using lymph node expansion, temperature, and blood parameters as correlates. As predicted, the faster growing clone was found to produce higher virulence. Mixed infections did not show higher virulence than single-clone infections, but interactions within mixed infections resulted in more transmission stage production than seen in either of the single-clone infections. Index Descriptors and Abbreviations. Theileria annulata, Apicomplexa, mixed infections, virulence, growth rates, red blood cell, RBC; packed cell volume, PCV.

VIRULENCE OF MIXED-CLONE AND SINGLE-CLONE INFECTIONS OF THE RODENT MALARIA PLASMODIUM CHABAUDI.

Most evolutionary models treat virulence as an unavoidable consequence of microparasite replication and have predicted that in mixed-genotype infections, natural selection should favor higher levels of virulence than is optimal in genetically uniform infections. Increased virulence may evolve as a genetically fixed strategy, appropriate for the frequency of mixed infections in the population, or may occur as a conditional response to mixed infection, that is, a facultative strategy. Here we test whether facultative alterations in replication rates in the presence of competing genotypes occur and generate greater virulence. An important alternative, not currently incorporated in models of the evolution of virulence, is that host responses mounted against genetically diverse parasites may be more costly or less effective than those against genetically uniform parasites. If so, mixed clone infections will be more virulent for a given parasite replication rate. Two groups of mice were infected with one of two clones of Plasmodium chabaudi parasites, and three groups of mice were infected with 1:9, 5:5, or 9:1 mixtures of the same two clones. Virulence was assessed by monitoring mouse body weight and red blood cell density. Transmission stage densities were significantly higher in mixed- than in single-clone infections. Within treatment groups, transmission stage production increased with the virulence of the infection, a phenotypic correlation consistent with the genetic correlation assumed by much of the theoretical work on the evolution of virulence. Consistent with theoretical predictions of facultative alterations in virulence, we found that mice infected with both parasite clones lost more weight and had on average lower blood counts than those infected with single-clone infections. However, there was no consistent evidence of the mechanism invoked by evolutionary models that predict this effect. Replication rates and parasite densities were not always higher in ∗∗∗mixed-clone infections, and for a given replication rate or parasite density, mixed-clone infections were still more virulent. Instead, prolonged anemia and increased transmission may have occured because genetically diverse infections are less rapidly cleared by hosts. Differences in maximum weight loss occured even when there were comparable parasite densities in mixed- and single-clone infections. We suggest that mounting an immune response against more that one parasite genotype is more costly for hosts, which therefore suffer higher virulence.