Health system capacity in Sydney, Australia in the event of a biological attack with smallpox

Planning for a re-emergent epidemic of smallpox requires surge capacity of space, resources and personnel within health systems. There are many uncertainties in such a scenario, including likelihood and size of an attack, speed of response and health system capacity. We used a model for smallpox transmission to determine requirements for hospital beds, contact tracing and health workers (HCWs) in Sydney, Australia, during a modelled epidemic of smallpox. Sensitivity analysis was done on attack size, speed of response and proportion of case isolation and contact tracing. We estimated 100638 clinical HCWs and 14595 public hospital beds in Sydney. Rapid response, case isolation and contact tracing are influential on epidemic size, with case isolation more influential than contact tracing. With 95% of cases isolated, outbreak control can be achieved within 100 days even with only 50% of contacts traced. However, if case isolation and contact tracing both fall to 50%, epidemic control is lost. With a smaller initial attack and a response commencing 20 days after the attack, health system impacts are modest. The requirement for hospital beds will vary from up to 4% to 100% of all available beds in best and worst case scenarios. If the response is delayed, or if the attack infects 10000 people, all available beds will be exceeded within 40 days, with corresponding surge requirements for clinical health care workers (HCWs). We estimated there are 330 public health workers in Sydney with up to 940,350 contacts to be traced. At least 3 million respirators will be needed for the first 100 days. To ensure adequate health system capacity, rapid response, high rates of case isolation, excellent contact tracing and vaccination, and protection of HCWs should be a priority. Surge capacity must be planned. Failures in any of these could cause health system failure, with inadequate beds, quarantine spaces, personnel, PPE and inability to manage other acute health conditions

How Valid Are Assumptions about Re-emerging Smallpox? A Systematic Review of Parameters Used in Smallpox Mathematical Models

Background: Globally eradicated in 1980, smallpox is listed as a category A bioterrorism agent. If smallpox were to re-emerge, it may be due to an act of bioterrorism or a laboratory accident, and the impact is likely to be severe. Preparedness against smallpox is subject to more uncertainty than other infectious diseases because it is eradicated, there is uncertainty about population immunity, and the current global health workforce has no practical experience or living memory of smallpox. In the event of re-emergence of smallpox, mathematical modeling plays a crucial role in improving the evidence base to inform preparedness, mitigation, and response activities. However, the predictions of mathematical models about outbreak magnitude and impact depend critically on the assumptions and disease parameters used. We aimed to identify modeling studies that would be applicable to re-emerging smallpox and to evaluate consistency and the certainty of the evidence published about the key parameters used. Methods: We conducted a systematic review using PRISMA criteria, of assumptions used in modeling studies on duration of latent, prodromal, and infectious period, as well as the choice of the basic reproduction number (R0) for re-emerging smallpox. We performed a literature search using PubMED, Scopus, Web of Science, and EMBASE and included peer-reviewed articles that focused on smallpox models, stated at least three of the aforementioned parameters and published in English. Findings: A total of 42 studies were selected for inclusion. There was general agreement on the duration of latent and prodromal periods, being 11-12 d (88%) and 3 d (59%), respectively. The duration of the infectious period varied from 4 to 20 d. Most models assumed 16 d (19%), 12 d (16.7%), and 8.6 d (12%) of infectiousness. In 25/34 studies, R0 ranged between 3 and 5, generally lower than the R0 calculated from past outbreaks. Discussion: Models of smallpox re-emergence also tend to use the same limited available historical data sources but assume a wide range of different estimates for key parameters. Models use very optimistic assumptions of decreased population immunity, despite high uncertainty about duration and magnitude of postvaccination immunity. This review reveals a paradox. A substantial proportion of the modern population is unvaccinated, never exposed to boosting from wild-type smallpox, or immunocompromised; furthermore, vaccine-induced immunity wanes over time. Failure to consider these factors in a model will lead to underestimating the true impact of a re-emergent smallpox epidemic in the contemporary population

Differential expression of basal microRNAs' patterns in human dental pulp stem cells

MicroRNAs (miRNAs) are small non-coding RNAs that regulate translation of mRNA into protein and play a crucial role for almost all biological activities. However, the identification of miRNAs from mesenchymal stem cells (MSCs), especially from dental pulp, is poorly understood. In this study, dental pulp stem cells (DPSCs) were characterized in terms of their proliferation and differentiation capacity. Furthermore, 104 known mature miRNAs were profiled by using real-time PCR. Notably, we observed 19 up-regulated miRNAs and 29 significantly down-regulated miRNAs in DPSCs in comparison with bone marrow MSCs (BM-MSCs). The 19 up-regulated miRNAs were subjected to ingenuity analysis, which were composed into 25 functional networks. We have chosen top 2 functional networks, which comprised 10 miRNA (hsa-miR-516a-3p, hsa-miR-125b-1-3p, hsa-miR-221-5p, hsa-miR-7, hsa-miR-584-5p, hsa-miR-190a, hsa-miR-106a-5p, hsa-mir-376a-5p, hsa-mir-377-5p and hsa-let-7f-2-3p). Prediction of target mRNAs and associated biological pathways regulated by each of this miRNA was carried out. We paid special attention to hsa-miR-516a-3p and hsa-miR-7-5p as these miRNAs were highly expressed upon validation with qRT-PCR analysis. We further proceeded with loss-of-function analysis with these miRNAs and we observed that hsa-miR-516a-3p knockdown induced a significant increase in the expression of WNT5A. Likewise, the knockdown of hsa-miR-7-5p increased the expression of EGFR. Nevertheless, further validation revealed the role of WNT5A as an indirect target of hsa-miR-516a-3p. These results provide new insights into the dynamic role of miRNA expression in DPSCs. In conclusion, using miRNA signatures in human as a prediction tool will enable us to elucidate the biological processes occurring in DPSCs

Quantification of Mesenchymal Stem Cell Growth Rates through Secretory and Excretory Biomolecules in Conditioned Media via Fresnel Reflection

An efficient and low cost optical method for directly measuring the concentration of homogenous biological solutes is proposed and demonstrated. The proposed system operates by Fresnel reflection, with a flat-cleaved single-mode fiber serving as the sensor probe. A laser provides a 12.9 dBm sensor signal at 1,550 nm, while a computer-controlled optical power meter measures the power of the signal returned by the probe. Three different mesenchymal stem cell (MSC) lines were obtained, sub-cultured and trypsinized daily over 9 days. Counts were measured using a haemocytometer and the conditioned media (CM) was collected daily and stored at −80 °C. MSCs release excretory biomolecules proportional to their growth rate into the CM, which changes the refractive index of the latter. The sensor is capable of detecting changes in the number of stem cells via correlation to the change in the refractive index of the CM, with the measured power loss decreasing approximately 0.4 dB in the CM sample per average 1,000 cells in the MSC subculture. The proposed system is highly cost-effective, simple to deploy, operate, and maintain, is non-destructive, and allows reliable real-time measurement of various stem cell proliferation parameters