Incorporating tick feeding behaviour into R0 for tick-borne pathogens.

Tick-borne pathogens pose a considerable disease burden in Europe and North America, where increasing numbers of human cases and the emergence of new tick-borne pathogens has renewed interest in resolving the mechanisms underpinning their geographical distribution and abundance. For Borrelia burgdorferi and tick-borne encephalitis (TBE) virus, transmission of infection from one generation of ticks to another occurs when older nymphal ticks infect younger larval ticks feeding on the same host, either indirectly via systemic infection of the vertebrate host or directly when feeding in close proximity. Here, expressions for the basic reproduction number, R0, and the related tick type-reproduction number, T, are derived that account for the observation that larval and nymphal ticks tend to aggregate on the same minority of hosts, a tick feeding behaviour known as co-aggregation. The pattern of tick blood meals is represented as a directed, acyclic, bipartite contact network, with individual vertebrate hosts having in-degree, kin, and out-degree, kout, that respectively represent cumulative counts of nymphal and larval ticks fed over the lifetime of the host. The in- and out-degree are not independent when co-aggregation occurs such that [Formula: see text] where 〈.〉 indicates expected value. When systemic infection in the vertebrate host is the dominant transmission route R02=T, whereas when direct transmission between ticks co-feeding on the same host is dominant then R0=T and the effect of co-aggregation on R0 is more pronounced. Simulations of B. burgdorferi and TBE virus transmission on theoretical tick-mouse contact networks revealed that aggregation and co-aggregation have a synergistic effect on R0 and T, that co-aggregation always increases R0 and T, and that aggregation only increases R0 and T when larvae and nymphs also co-aggregate. Co-aggregation has the greatest absolute effect on R0 and T when the mean larval burden of hosts is high, and the largest relative effect on R0 for pathogens sustained by co-feeding transmission, e.g. TBE virus in Europe, compared with those predominantly spread by systemic infection, e.g. B. burgdorferi. For both pathogens, though, co-aggregation increases the mean number of ticks infected per infectious tick, T, and so too the likelihood of pathogen persistence.

Virtual reality as complementary pain therapy in hospitalized patients with sickle cell disease.

OBJECTIVE: Due to incomplete management of vaso-occlusive pain episodes (VOE) in patients with sickle cell disease (SCD), we sought to determine if immersive VR would be feasible for inpatients. Secondarily, we hypothesized that a single VR session would improve the VOE pain experience. PROCEDURES: Consecutive patients with SCD eight years and older admitted for VOE were offered one 15-minute VR session, utilizing a relaxing underwater world specifically created for pediatric patients and to minimize potential simulator side effects. Safety and acceptability were evaluated with a brief survey before and after the session. Pain was evaluated utilizing the validated adolescent pediatric pain tool (APPT). Survey data and pain scores were analyzed using Wilcoxon signed-rank test as the data were nonnormally distributed. RESULTS: Thirty patients, 21 female, with a median age of 16 years were enrolled, the majority having hemoglobin SS disease. The VR session had no reported side effects; all patients requested VR again in the future. Median pain intensity (pre-VR 7.3 [interquartile range, IQR, 6.1, 8.8], post-VR 5.8 [4.7, 7.9]), number of affected body areas (pre-VR 3.0 [2.0, 7.8], post-VR 2.0 [0, 4.8]), and qualitative measures including sensory, affective, evaluative, and temporal pain domains were all statistically reduced (i.e., P ≤0.01). CONCLUSIONS: VR therapy was feasible in a cohort of patients with SCD admitted for VOE. In addition to standard therapies, VR may help reduce the pain experience with SCD VOE. Further study is required to determine the impact of VR therapy on opioid usage and length of stay in hospital.

Assessing the impact of Australia's mass vaccination campaigns over the Delta and Omicron outbreaks.

BACKGROUND: The Australian Government implemented a national vaccination campaign against COVID-19 beginning February 22, 2021. The roll-out was criticised for being delayed relative to many high-income countries, but high levels of vaccination coverage were belatedly achieved. The large-scale Omicron outbreak in January 2022 resulted in a massive number of cases and deaths, although mortality would have been far higher if not for vigorous efforts to rapidly vaccinate the entire population. The impact of the vaccination coverage was assessed over this extended period. METHODS: We considered NSW, as the Australian jurisdiction with the highest quality data for our purposes and which still reflected the national experience. Weekly death rates were derived among individuals aged 50+ with respect to vaccine status between August 8, 2021 and July 9, 2022. We evaluated deaths averted by the vaccination campaign by modelling alternative counterfactual scenarios based on a simple data-driven modelling methodology presented by Jia et al. (2023). FINDINGS: Unvaccinated individuals had a 7.7-fold greater mortality rate than those who were fully vaccinated among people aged 50+, which rose to 11.2-fold in those who had received a booster dose. If NSW had fully vaccinated its ~2.9 million 50+ residents earlier (by July 28, 2021), only 440 of the total 3,495 observed 50+ deaths would have been averted. Up to July 9, 2022, the booster campaign prevented 1,860 deaths. In the absence of a vaccination campaign, ~21,250 COVID-19 50+ deaths (conservative estimate) could have been expected in NSW i.e., some 6 times the actual total. We also find the methodology of Jia et al. (2023) can sometimes significantly underestimate that actual number. INTERPRETATION: The Australian vaccination campaign was successful in reducing mortality over 2022, relative to alternative hypothetical vaccination scenarios. The success was attributable to the Australian public's high levels of engagement with vaccination in the face of new SARS-COV-2 variants, and because high levels of vaccination coverage (full and booster) were achieved in the period shortly before the major Omicron outbreak of 2022.

Transmission elasticity in communities hyperendemic for tuberculosis.

BACKGROUND: Despite consistently meeting international performance targets for tuberculosis case detection and treatment success, areas where tuberculosis is hyperendemic fail to achieve the predicted epidemiological impact. In this article, we explore the anomalous relationship between defined performance targets and actual reduction in tuberculosis transmission. METHODS: In areas where tuberculosis is endemic, poorly ventilated social gathering places such as shebeens (informal alcohol drinking places), minibus taxis, and clinic waiting rooms are all potential transmission hot spots. We modeled the transmission reduction achieved by removal of infectious persons in settings with different tuberculosis prevalence rates to demonstrate the concept of transmission elasticity. We then applied this concept to real-life data from a hyperendemic community in Cape Town, South Africa. RESULTS: In a hyperendemic area, reducing the number of infectious people by a given percentage results in a smaller percentage decrease in the annual risk of infection (ARI) compared with a nonendemic area; for example, removing 10% of infectious persons could result in as little as a 5% reduction in the ARI. With use of real-life data and removal of 60% of infectious individuals with tuberculosis, as would be achieved by meeting current performance targets of 70% case detection and 85% cure, the estimated ARI reduction is 50%. CONCLUSIONS: The relationship between the number of infectious people removed and the decrease in ARI is nonlinear. The concept of transmission elasticity has important implications for the formulation of universal performance targets, since hyperendemic areas would require more stringent targets to achieve comparable transmission reduction.

Social mixing patterns within a South African township community: implications for respiratory disease transmission and control.

A prospective survey of social mixing patterns relevant to respiratory disease transmission by large droplets (e.g., influenza) or small droplet nuclei (e.g., tuberculosis) was performed in a South African township in 2010. A total of 571 randomly selected participants recorded the numbers, times, and locations of close contacts (physical/nonphysical) and indoor casual contacts met daily. The median number of physical contacts was 12 (interquartile range (IQR), 7-18), the median number of close contacts was 20 (IQR, 13-29), and the total number of indoor contacts was 30 (IQR, 12-54). Physical and close contacts were most frequent and age-associative in youths aged 5-19 years. Numbers of close contacts were 40% higher than in corresponding populations in industrialized countries (P < 0.001). This may put township communities at higher risk for epidemics of acute respiratory illnesses. Simulations of an acute influenza epidemic predominantly involved adolescents and young adults, indicating that control strategies should be directed toward these age groups. Of all contacts, 86.2% occurred indoors with potential exposure to respiratory droplet nuclei, of which 27.2%, 20.1%, 20.0%, and 8.0% were in transport, own household, crèche/school, and work locations, respectively. Indoor contact time was long in households and short during transport. High numbers of indoor contacts and intergenerational mixing in households and transport may contribute to exceptionally high rates of tuberculosis transmission reported in the community.

Tuberculosis transmission to young children in a South African community: modeling household and community infection risks.

BACKGROUND: Tuberculosis transmission is determined by contact between infectious and susceptible individuals. A recent study reported a 4% annual risk of child tuberculosis infection in a southern African township. A model was used to explore the interactions between prevalence of adult tuberculosis infection, adult-to-child contacts, and household ventilation, which could result in such a high annual risk of tuberculosis infection. METHODS: Number of residents per household and tuberculosis incidence were derived from a household census and community tuberculosis registers. Using the Wells-Riley equation and probability analyses of contact between infectious adults with tuberculosis and preschool children, we estimated the annual risk of tuberculosis infection within and outside of the home. RESULTS: There was a mean of 2.2 adults per child-containing household with a 1.35% annual adult smear-positive tuberculosis notification rate. The maximal household annual risk of tuberculosis infection was 3%, which was primarily determined by the number of resident adults. Transmission risk outside the home increased with increasing number of households visited. Transmission probabilities were sensitive to exposure time, ventilation, and period of adult infectivity. The benefits of increased ventilation were greatest when the period of infectivity was reduced. Similar reductions in household transmission could be achieved by increasing ventilation from 2 to 6 air changes/hour or by separating child and adult sleeping areas. CONCLUSIONS: The annual risk of tuberculosis infection of preschool children predominantly results from infectious residents in the home. However, even with limited social interactions, a substantial proportion of transmissions may occur from nonresident adults. The benefits of increased ventilation are maximized when the period of infectivity is reduced by prompt treatment of source cases.

Usability Testing of an Interactive Virtual Reality Distraction Intervention to Reduce Procedural Pain in Children and Adolescents With Cancer [Formula: see text].

PURPOSE: Needle procedures are among the most distressing aspects of pediatric cancer-related treatment. Virtual reality (VR) distraction offers promise for needle-related pain and distress given its highly immersive and interactive virtual environment. This study assessed the usability (ease of use and understanding, acceptability) of a custom VR intervention for children with cancer undergoing implantable venous access device (IVAD) needle insertion. METHOD: Three iterative cycles of mixed-method usability testing with semistructured interviews were undertaken to refine the VR. RESULTS: Participants included 17 children and adolescents (8-18 years old) with cancer who used the VR intervention prior to or during IVAD access. Most participants reported the VR as easy to use (82%) and understand (94%), and would like to use it during subsequent needle procedures (94%). Based on usability testing, refinements were made to VR hardware, software, and clinical implementation. Refinements focused on increasing responsiveness, interaction, and immersion of the VR program, reducing head movement for VR interaction, and enabling participant alerts to steps of the procedure by clinical staff. No adverse events of nausea or dizziness were reported. CONCLUSIONS: The VR intervention was deemed acceptable and safe. Next steps include assessing feasibility and effectiveness of the VR intervention for pain and distress.

Predicted Spatial Spread of Canine Rabies in Australia.

Modelling disease dynamics is most useful when data are limited. We present a spatial transmission model for the spread of canine rabies in the currently rabies-free wild dog population of Australia. The introduction of a sub-clinically infected dog from Indonesia is a distinct possibility, as is the spillover infection of wild dogs. Ranges for parameters were estimated from the literature and expert opinion, or set to span an order of magnitude. Rabies was judged to have spread spatially if a new infectious case appeared 120 km from the index case. We found 21% of initial value settings resulted in canine rabies spreading 120km, and on doing so at a median speed of 67 km/year. Parameters governing dog movements and behaviour, around which there is a paucity of knowledge, explained most of the variance in model outcomes. Dog density, especially when interactions with other parameters were included, explained some of the variance in whether rabies spread 120km, but dog demography (mean lifespan and mean replacement period) had minimal impact. These results provide a clear research direction if Australia is to improve its preparedness for rabies.

Systematic Population Screening, Using Biomarkers and Genetic Testing, Identifies 2.5% of the U.K. Pediatric Diabetes Population With Monogenic Diabetes.

OBJECTIVE: Monogenic diabetes is rare but is an important diagnosis in pediatric diabetes clinics. These patients are often not identified as this relies on the recognition of key clinical features by an alert clinician. Biomarkers (islet autoantibodies and C-peptide) can assist in the exclusion of patients with type 1 diabetes and allow systematic testing that does not rely on clinical recognition. Our study aimed to establish the prevalence of monogenic diabetes in U.K. pediatric clinics using a systematic approach of biomarker screening and targeted genetic testing. RESEARCH DESIGN AND METHODS: We studied 808 patients (79.5% of the eligible population) <20 years of age with diabetes who were attending six pediatric clinics in South West England and Tayside, Scotland. Endogenous insulin production was measured using the urinary C-peptide creatinine ratio (UCPCR). C-peptide-positive patients (UCPCR ≥0.2 nmol/mmol) underwent islet autoantibody (GAD and IA2) testing, with patients who were autoantibody negative undergoing genetic testing for all 29 identified causes of monogenic diabetes. RESULTS: A total of 2.5% of patients (20 of 808 patients) (95% CI 1.6-3.9%) had monogenic diabetes (8 GCK, 5 HNF1A, 4 HNF4A, 1 HNF1B, 1 ABCC8, 1 INSR). The majority (17 of 20 patients) were managed without insulin treatment. A similar proportion of the population had type 2 diabetes (3.3%, 27 of 808 patients). CONCLUSIONS: This large systematic study confirms a prevalence of 2.5% of patients with monogenic diabetes who were <20 years of age in six U.K. clinics. This figure suggests that ∼50% of the estimated 875 U.K. pediatric patients with monogenic diabetes have still not received a genetic diagnosis. This biomarker screening pathway is a practical approach that can be used to identify pediatric patients who are most appropriate for genetic testing.

Antiretroviral therapy initiated soon after HIV diagnosis as standard care: potential to save lives?

In 2008, an estimated 33.4 million people were infected with human immunodeficiency virus (HIV) and ~4 million people were receiving antiretroviral therapy (ART). However, in 2007, an estimated 6.7 million people were in need of ART under the current World Health Organization guidelines, and 2.7 million more people became infected with HIV. Most of those not currently eligible for ART will become eligible within the next decade, making the current treatment strategy unsustainable. The development of cheaper, less toxic, and more potent antiretrovirals over the past decade has made it possible to consider novel strategies of arresting the HIV/AIDS epidemic. Evidence is growing that ART can be used to prevent HIV transmission and that earlier initiation of treatment is beneficial for those infected with HIV. A mathematical model predicts that by testing whole communities annually and treating all who are infected immediately, up to 7.2 million AIDS-related deaths could be prevented in the next 40 years, long-term funding required to fight the HIV epidemic could be reduced, and, most importantly, control of the HIV/ AIDS epidemic could be regained within 1-2 years of full-scale implementation of the strategy. We discuss the development of the concept of ART for the prevention of HIV transmission and the modeled impact that a test-and-treat strategy could have on the HIV epidemic, and consequently argue that a field trial should be carried out to confirm model parameters, highlight any practical problems, and test the model's predictions.

Tuberculosis control has failed in South Africa--time to reappraise strategy.

South Africa's rate of tuberculosis (TB) has increased over the last 20 years, to now having the third-highest TB burden in the world. The TB control programme has primarily focused on effective case management of passively presenting TB cases, and progress has been recorded towards international treatment targets. While outcomes for notified TB cases have improved, this strategy failed to contain the TB epidemic. South Africa has the highest per capita annual risk of TB disease of comparably sized countries globally, and its communities have extremely high TB transmission rates. The rates of TB infection of children and adolescents are now similar to those reported 100 years ago in Europe long before chemotherapy became available. High rates of HIV testing of TB patients in Cape Town allows analysis of TB notification data stratified by age, type of TB and HIV status, and a better understanding of TB epidemiology. TB infection prevalence data from Cape Town communities allow estimation of the prevailing force of TB infection and, together with TB notification and prevalence data, the effective number of secondary infections and case finding proportions can be estimated. This better understanding of the major drivers of the TB epidemic allows reasons to be identified for failure of the present strategy. New control strategies can also be identified, that must be accompanied by novel TB control targets.

Tuberculosis in a South African prison - a transmission modelling analysis.

BACKGROUND: Prisons are recognised internationally as institutions with very high tuberculosis (TB) burdens where transmission is predominantly determined by contact between infectious and susceptible prisoners. A recent South African court case described the conditions under which prisoners awaiting trial were kept. With the use of these data, a mathematical model was developed to explore the interactions between incarceration conditions and TB control measures. METHODS: Cell dimensions, cell occupancy, lock-up time, TB incidence and treatment delays were derived from court evidence and judicial reports. Using the Wells-Riley equation and probability analyses of contact between prisoners, we estimated the current TB transmission probability within prison cells, and estimated transmission probabilities of improved levels of case finding in combination with implementation of national and international minimum standards for incarceration. RESULTS: Levels of overcrowding (230%) in communal cells and poor TB case finding result in annual TB transmission risks of 90% per annum. Implementing current national or international cell occupancy recommendations would reduce TB transmission probabilities by 30% and 50%, respectively. Improved passive case finding, modest ventilation increase or decreased lock-up time would minimally impact on transmission if introduced individually. However, active case finding together with implementation of minimum national and international standards of incarceration could reduce transmission by 50% and 94%, respectively. CONCLUSIONS: Current conditions of detention for awaiting-trial prisoners are highly conducive for spread of drug-sensitive and drug-resistant TB. Combinations of simple well-established scientific control measures should be implemented urgently.

Calculating the required transfusion volume in children.

BACKGROUND: The traditional method of calculating blood volume for pediatric transfusion in the UK is weight (kg) x aimed increment in hemoglobin concentration (Hb; g/dL) x the transfusion factor, usually quoted at 3 or 4. This equation is without evidence base. The aim was to assess how the volume of red cells (RBCs) affects the increase in serum Hb in children and to devise a formula that allows accurate volume calculation. STUDY DESIGN AND METHODS: All pediatric intensive care charts for 2 years were examined retrospectively. The immediate pre- and posttransfusion Hb estimations and the precise volumes of RBC transfused were recorded. Fluid boluses and hemorrhagic loss during the transfusion were documented. RESULTS: A total of 7679 patient charts were examined with a total of 564 transfusions. All patients who were bleeding, had drain losses, or had concurrent colloid infusions were excluded, giving 379 data points. The correlation gradient between mL per kg blood transfused and increase in Hb was 5.02. There was no significant association between effect and patient weight, age, starting Hb, transfusion time, or sex. No significant difference was found in Hb at 1 and 7 hours posttransfusion. CONCLUSIONS: The following equation should be used to calculate transfusion volumes: weight (kg) x increment in Hb (g/dL) x 3/(hematocrit [Hct] level of RBCs). This predicts that with a UK standard Hct of 0.6, 10 mL/kg gives an increment of 2 g/dL. Care must be taken not to risk hypervolemia, while minimizing donor exposure. Hb estimation 1 hour after transfusion is the same as 7 hours after transfusion.

Resuscitation and anaesthesia for penetrating trauma.

PURPOSE OF REVIEW: The worldwide burden of trauma is increasing, but is unequal between nations. Trauma targets the young and productive in society and imposes a major burden on the health infrastructure. This review provides a distillation of practice in a busy urban trauma centre dealing with large volumes of penetrating trauma. RECENT FINDINGS: The anaesthetist holds a pivotal role in the management of penetrating injury; the requirements of prompt airway control, early delivery to theatre and control of a physiologically brittle patient can be challenging. Recognition that attempts at definitive surgery in exsanguinating patients may do more harm than good has made surgery a tool of resuscitation rather than an end in itself. SUMMARY: Depending on where they practice, clinicians are more or less likely to encounter patients with gunshot wounds. However, adherence to basic principles and attention to the details of temperature control, invasive haemodynamic monitoring, blood product therapy and effective communication should translate to improved outcomes for patients after penetrating trauma.