Ebola cases and health system demand in Liberia.

In 2014, a major epidemic of human Ebola virus disease emerged in West Africa, where human-to-human transmission has now been sustained for greater than 12 months. In the summer of 2014, there was great uncertainty about the answers to several key policy questions concerning the path to containment. What is the relative importance of nosocomial transmission compared with community-acquired infection? How much must hospital capacity increase to provide care for the anticipated patient burden? To which interventions will Ebola transmission be most responsive? What must be done to achieve containment? In recent years, epidemic models have been used to guide public health interventions. But, model-based policy relies on high quality causal understanding of transmission, including the availability of appropriate dynamic transmission models and reliable reporting about the sequence of case incidence for model fitting, which were lacking for this epidemic. To investigate the range of potential transmission scenarios, we developed a multi-type branching process model that incorporates key heterogeneities and time-varying parameters to reflect changing human behavior and deliberate interventions in Liberia. Ensembles of this model were evaluated at a set of parameters that were both epidemiologically plausible and capable of reproducing the observed trajectory. Results of this model suggested that epidemic outcome would depend on both hospital capacity and individual behavior. Simulations suggested that if hospital capacity was not increased, then transmission might outpace the rate of isolation and the ability to provide care for the ill, infectious, and dying. Similarly, the model suggested that containment would require individuals to adopt behaviors that increase the rates of case identification and isolation and secure burial of the deceased. As of mid-October, it was unclear that this epidemic would be contained even by 99% hospitalization at the planned hospital capacity. A new version of the model, updated to reflect information collected during October and November 2014, predicts a significantly more constrained set of possible futures. This model suggests that epidemic outcome still depends very heavily on individual behavior. Particularly, if future patient hospitalization rates return to background levels (estimated to be around 70%), then transmission is predicted to remain just below the critical point around Reff = 1. At the higher hospitalization rate of 85%, this model predicts near complete elimination in March to June, 2015.

Multi-scale model of epidemic fade-out: Will local extirpation events inhibit the spread of white-nose syndrome?

White-nose syndrome (WNS) is an emerging infectious disease that has resulted in severe declines of its hibernating bat hosts in North America. The ongoing epidemic of white-nose syndrome is a multi-scale phenomenon becau.se it causes hibernaculum-level extirpations, while simultaneously spreading over larger spatial scales. We investigate a neglected topic in ecological epidemiology: how local pathogen-driven extirpations impact large-scale pathogen spread. Previous studies have identified risk factors for propagation of WNS over hibernaculum and landscape scales but none of these have tested the hypothesis that separation of spatial scales and disease-induced mortality at the hibernaculum level might slow or halt its spread. To test this hypothesis, we developed a mechanistic multi-scale model parameterized using white-nose syndrome.county and site incidence data that connects hibernaculum-level susceptible-infectious-removed (SIR) epidemiology to the county-scale contagion process. Our key result is that hibernaculum-level extirpations will not inhibit county-scale spread of WNS. We show that over 80% of counties of the contiguous USA are likely to become infected before the current epidemic is over and that geometry of habitat connectivity is such that host refuges are exceedingly rare. The macroscale spatiotemporal infection pattern that emerges from local SIR epidemiological processes falls within a narrow spectrum of possible outcomes, suggesting that recolonization, rescue effects, and multi-host complexities at local scales are not important to forward propagation of WNS at large spatial scales. If effective control measures are not implemented, precipitous declines in bat populations are likely, particularly in cave-dense regions that constitute the main geographic corridors of the USA, a serious concern for bat conservation.

The effect of seasonal birth pulses on pathogen persistence in wild mammal populations.

The notion of a critical community size (CCS), or population size that is likely to result in long-term persistence of a communicable disease, has been developed based on the empirical observations of acute immunizing infections in human populations, and extended for use in wildlife populations. Seasonal birth pulses are frequently observed in wildlife and are expected to impact infection dynamics, yet their effect on pathogen persistence and CCS have not been considered. To investigate this issue theoretically, we use stochastic epidemiological models to ask how host life-history traits and infection parameters interact to determine pathogen persistence within a closed population. We fit seasonal birth pulse models to data from diverse mammalian species in order to identify realistic parameter ranges. When varying the synchrony of the birth pulse with all other parameters being constant, our model predicted that the CCS can vary by more than two orders of magnitude. Tighter birth pulses tended to drive pathogen extinction by creating large amplitude oscillations in prevalence, especially with high demographic turnover and short infectious periods. Parameters affecting the relative timing of the epidemic and birth pulse peaks determined the intensity and direction of the effect of pre-existing immunity in the population on the pathogen's ability to persist beyond the initial epidemic following its introduction.

Leveraging epidemiology as a decision support tool during the COVID-19 epidemic in South Africa.

By May 2021, South Africa (SA) had experienced two 'waves' of COVID-19 infections, with an initial peak of infections reached in July 2020, followed by a larger peak of infections in January 2021. Public health decisions rely on accurate and timely disease surveillance and epidemiological analyses, and accessibility of data at all levels of government is critical to inform stakeholders to respond effectively. In this paper, we describe the adaptation, development and operation of epidemiological surveillance and modelling systems in SA in response to the COVID-19 epidemic, including data systems for monitoring laboratory-confirmed COVID-19 cases, hospitalisations, mortality and recoveries at a national and provincial level, and how these systems were used to inform modelling projections and public health decisions. Detailed descriptions on the characteristics and completeness of individual datasets are not provided in this paper. Rapid development of robust data systems was necessary to support the response to the SA COVID-19 epidemic. These systems produced data streams that were used in decision-making at all levels of government. While much progress was made in producing epidemiological data, challenges remain to be overcome to address gaps to better prepare for future waves of COVID-19 and other health emergencies.

Mind the gap: Patterns of red blood cell product usage in South Africa, 2014 - 2019.

BACKGROUND: A key component of any successful healthcare system is the availability of sufficient, safe blood products delivered in an equitable manner. South Africa (SA) has a two-tiered healthcare system with public and privately funded sectors. Blood utilisation data for both sectors are lacking. Evaluation of blood utilisation patterns in each healthcare sector will enable implementation of systems to bring about more equality. OBJECTIVES: To conduct a critical evaluation of red blood cell (RBC) product utilisation patterns at the South African National Blood Service (SANBS). METHODS: Operationally collected data from RBC requests submitted to SANBS blood banks for the period 1 January 2014 - 31 March 2019 were used to determine temporal RBC product utilisation patterns by healthcare sector. Demographic patterns were determined, and per capita RBC utilisation trends calculated. RESULTS: Of the 2 356 441 transfusion events, 65.9% occurred in the public and 34.1% in the private sector. Public sector patients were younger (median (interquartile range (IQR)) 33 (22 - 49) years) than in the private sector (median (IQR) 54 (37 - 68) years), and mainly female in both sectors (66.2% in the public sector and 53.4% in the private sector). Between 2014 and 2018, per capita RBC utilisation decreased from 11.9 to 11.0/1 000 population in the public sector, but increased from 34.8 to 38.2/1 000 population in the private sector. CONCLUSIONS: We confirmed distinctly different RBC utilisation patterns between the healthcare sectors in SA. Possible drivers for these differences may be healthcare access, differing patient populations and prescriber habits. Better understanding of these drivers may help inform equitable public health policy.

Spatial spread of the West Africa Ebola epidemic.

Controlling Ebola outbreaks and planning an effective response to future emerging diseases are enhanced by understanding the role of geography in transmission. Here we show how epidemic expansion may be predicted by evaluating the relative probability of alternative epidemic paths. We compared multiple candidate models to characterize the spatial network over which the 2013-2015 West Africa epidemic of Ebola virus spread and estimate the effects of geographical covariates on transmission during peak spread. The best model was a generalized gravity model where the probability of transmission between locations depended on distance, population density and international border closures between Guinea, Liberia and Sierra Leone and neighbouring countries. This model out-performed alternative models based on diffusive spread, the force of infection, mobility estimated from cell phone records and other hypothesized patterns of spread. These findings highlight the importance of integrated geography to epidemic expansion and may contribute to identifying both the most vulnerable unaffected areas and locations of maximum intervention value.

Removal of therapeutic drugs by continuous arteriovenous hemofiltration.

Plasma and ultrafiltrate drug concentrations were determined for 17 drugs in ten patients receiving continuous arteriovenous hemofiltration. Ultrafiltrate concentrations were not always predictable because of multiple factors, which may include altered drug-protein binding in these very ill patients.

CNS angiitis in graft vs host disease.

Graft-vs-host disease (GVHD) is a potentially treatable cause of progressive neurologic decline after bone marrow transplantation (BMT). The authors present histologic confirmation of CNS granulomatous angiitis in a child with chronic GVHD after BMT. Since cranial MRI showed only nonspecific findings, CNS vasculitis associated with GVHD after BMT may be underdiagnosed.

Anuric renal failure from massive bilateral renal hematoma following extracorporeal shock wave lithotripsy.

We report a case of large bilateral perirenal and intrarenal hematoma formation leading to prolonged anuria in the absence of obstruction following extracorporeal shock wave lithotripsy. With conservative management, including the need for hemodialysis support, renal function gradually returned. A mechanism for this patient's anuric renal failure is postulated and caution is advised when considering simultaneous bilateral extracorporeal shock wave lithotripsy in patients with a potential risk of bleeding.

Diagnostic value of creatine kinase and creatine kinase MB isoenzyme in chronic hemodialysis patients: a longitudinal study.

Serial measurements of total creatine kinase (CK) and the MB isoenzyme of CK (CK-MB) were performed on 18 stable hemodialysis patients over a 36 month interval in a longitudinal study designed to examine CK and CK-MB variability. Total CK was measured by the DuPont ACA pack procedure. CK-MB was quantitated by the ACA CK-MB ion exchange pack procedure, and by electrophoresis. The mean CK level was 242 +/- 179 IU/l (+/- SD). The mean CK-MB level was approximately 8% of the total CK. Seventy-two percent of the patients had at least one elevated CK level during the course of this study. Depending upon the method of analysis, 88 to 100% of the patients had at least one elevated CK-MB level. Marked and sporadic variations in both total CK and CK-MB levels were apparent, but were not related to the assay. Patients receiving long-term intramuscular androgens had higher CK, but not CK-MB, than did hemodialysis patients not receiving these agents. Discontinuation of the intramuscular androgens for four weeks led to a fall in CK in only one of four patients. Therefore there appears to be a biological effect of exogenous androgens which may play a role in elevating CK in hemodialysis patients.

Effects of hyperglycemia and mannitol infusions on renal hemodynamics in normal subjects.

Early diabetes mellitus is characterized by an increase in glomerular filtration rate and effective renal plasma flow which may initiate and potentiate glomerular injury which ultimately results in diabetic nephropathy. To investigate the role of hyperglycemia per se in mediating these hemodynamic changes, eight healthy adults had inulin clearance, creatinine clearance, and para-aminohippurate (PAH) clearance after steady state conditions of hyperglycemia were achieved (549 +/- 86). Clearances were repeated during equivalent osmotic diuresis with Mannitol. Euvolemia was maintained by quantitative fluid and electrolyte replacement of urinary losses. Mean inulin clearances were 87 +/- 6, 87 +/- 5, and 81 +/- 4 ml/min during control, glucose, and mannitol periods (p = ns). Creatinine clearance overestimated inulin clearance by 15-32% but there were no differences between control glucose and mannitol periods. PAH clearance fell from control values of 595 +/- 29 to 340 +/- 22 ml/min during hyperglycemia (p less than .05). During osmotic diuresis with mannitol PAH, clearance rose to control values. In vitro studies excluded the possibility that conjugation between glucose and PAH can explain the clearance results. These results in normal subjects documenting renal vasoconstriction with hyperglycemia are of particular interest in view of recent experimental data suggesting that failure to vasoconstrict characterizes the hemodynamics of early diabetes.

Effects of arprinocid on developmental stages of Eimeria tenella.

Restricted medication experiments were done to correlate time of arprinocid medication with developmental stages of the life cycle of Eimeria tenella. By the criterion of histopathology and using a massive inoculum (10(6) sporulated oocysts), 50 ppm was partially active and 70 ppm was fully active against the first asexual generation when medication was delayed until day 1. When medication was delayed until day 2, full activity was demonstrated against the late, first asexual generation. When medication was delayed until day 3, definite but less complete activity was shown against the late, second asexual generation. Using the conventional efficacy parameters and with an inoculum of 5 X 10(4), full activity occurred with 50 ppm when medication was started up to day 2. Essentially full activity was observed with 60 ppm started at day 3. The combined results of the two tests are interpreted to indicate high activity against both the first and second asexual generations. Medication with 70 ppm changed the wall-forming bodies of the macrogamete. They were indistinct and less intensely eosinophilic than controls.

Histopathologic features of canine heartworm microfilarial infection after treatment with ivermectin.

Tissues of dogs treated with ivermectin were examined microscopically to learn the fate of microfilariae of canine heartworm that disappear from the peripheral circulation within a few days of treatment. Medicated dogs were killed 18 hours, 3 days, and 6 days after treatment with 0.5 mg of ivermectin/kg of body weight subcutaneously. Ivermectin was dissolved in 60% propylene glycol and 40% glycerol formal. In dogs killed at posttreatment hour 18, the peripheral microfilaremia had decreased by an average of 89%. At this time, a dense mass of RBC, WBC, and macrophages plus many microfilariae was found in pulmonary alveolar septae. Similar reactions were seen in liver, kidney, and spleen. Phagocytosis of microfilarial fragments was evident. In dogs killed at posttreatment day 3, many microfilariae were fragmented and phagocytosis of the fragments was common. In dogs killed at posttreatment day 6, microgranulomas were common, particularly in such vascular organs as lungs, kidney, and liver. Microgranulomas containing microfilariae were also seen in spleen, skeletal and cardiac muscles, diaphragm, lymph nodes, gastrointestinal tract, and pancreas. Small glial nodules were seen in the CNS. Denudation of the atrial epicardium was associated with fragments of microfilariae and granulomatous inflammatory cells. Renal epithelial crescents were observed in treated and nontreated dogs. Plasma cells were conspicuous in treated and nontreated dogs, especially in some livers and kidneys. Before treatment, all dogs were severely microfilaremic. At the end of the experiment, the peripheral microfilaremia was reduced by 98%.(ABSTRACT TRUNCATED AT 250 WORDS)

Safety study of a beef-based chewable tablet formulation of ivermectin and pyrantel pamoate in growing dogs, pups, and breeding adult dogs.

To determine the safety of a new combination of ivermectin and pyrantel (as pamoate salt) in a novel beef-based chewable tablet formulation, 3 tolerance trials were conducted and included growing dogs, pups, and breeding adult dogs. Growing dogs, given the combination orally for 5 consecutive days at recommended dosages (5 mg of pyrantel/kg of body weight, 6 micrograms of ivermectin/kg) or at twice the pyrantel dosage in combination with the recommended dosage of ivermectin, had no adverse effects. The combination also was administered to 6-week-old pups at 1, 3, and 5 times the recommended dose on 3 successive days for 3 times in 1 month. Compared with age-matched controls, treatment had no effect on clinical status, growth rate, or gross or histologic features. Breeding male and female dogs given the combination at 3 times the recommended dose for extended periods had no adverse effects, and prevalence of abnormalities in the offspring was not greater than that in nonmedicated controls.

Reproductive evaluation of male beagles and the safety of ivermectin.

Ivermectin had no adverse effects on spermatogenesis, fertility, or reproductive performance of Beagle dogs when administered orally at 600 micrograms/kg (0.6 mg/kg) of body weight monthly for 8 treatments. Semen was collected every 3 days from 28 days before treatment began until 83 days thereafter from 6 ivermectin-treated Beagles and 6 similar water-treated controls (38 collections/dog). All dogs were then bred to 2 nontreated bitches each; litter size, birth weights, and pup abnormalities and mortalities were evaluated. After all pups were whelped, each dog was euthanatized and necropsied, and the testis and epididymis were examined microscopically.

Analgesic-associated nephropathy. Unappreciated cause of renal dysfunction.

Analgesic-associated nephropathy is a preventable renal disease that leads to end-stage renal failure when it is not recognized and treated. Patients with this disorder are usually evaluated initially by the family physician, whose awareness of the entity and high degree of clinical suspicion will result in specific questioning regarding analgesic intake. A history of analgesic abuse, coupled with associated laboratory and radiologic abnormalities, usually suffices to make the diagnosis. A favorable prognosis is dependent on early diagnosis and discontinuation of all analgesic use.

Adenocarcinoma of the colon metastasizing to the foot masquerading as osteomyelitis.

The authors report an unusual case of adenocarcinoma of the colon metastasizing to the foot. The initial diagnosis of osteomyelitis based on clinical, radiographic, and radionuclide uptake findings led to improper prolonged treatment, resulting in a major complication. A diagnostic biopsy of the involved bone is essential in any case in which the clinical diagnosis is uncertain.

Effect of ivermectin on the reproductive potential of breeding rams.

Ivermectin was administered orally 6 times at 21d intervals at 400 micrograms/kg (double the recommended dosage) to 10 Merino rams. Ten other rams served as untreated controls. Semen samples were collected serially before and after each treatment, and evaluated for volume, density, colour, motility, pH, percentage live sperm and sperm morphology. One testis was removed from each ram 9d after the last treatment, and histological examinations were performed on testicular sections. The semen of the 2 groups was similar before the first and after the last treatments. The seminal pH of treated rams was lower during the periods following the first 5 treatments. The volume of ejaculates of treated rams was generally higher during the periods following the first 5 treatments, but not consistently so. No histological differences were observed in the testicular tissue of treated and control animals 9 days after the sixth treatment. It was concluded that repeated treatment with ivermectin at the recommended dosage of 200 micrograms/kg will not impair the reproductive potential of rams.

Spread of white-nose syndrome on a network regulated by geography and climate.

Wildlife and plant diseases can reduce biodiversity, disrupt ecosystem services and threaten human health. Emerging pathogens have displayed a variety of spatial spread patterns due to differences in host ecology, including diffusive spread from an epicentre (West Nile virus), jump dispersal on a network (foot-and-mouth disease), or a combination of these (Sudden oak death). White-nose syndrome is a highly pathogenic infectious disease of bats currently spreading across North America. Understanding how bat ecology influences this spread is crucial to management of infected and vulnerable populations. Here we show that white-nose syndrome spread is not diffusive but rather mediated by patchily distributed habitat and large-scale gradients in winter climate. Simulations predict rapid expansion and infection of most counties with caves in the contiguous United States by winter 2105-2106. Our findings show the unique pattern of white-nose syndrome spread corresponds to ecological traits of the host and suggest hypotheses for transmission mechanisms acting at the local scale.