Planning an Integrated Disease Surveillance and Response System: A Matrix of Skills and Activities

The threat of a global influenza pandemic and the adoption of the World Health Organization (WHO) International Health Regulations (2005) highlight the value of well-coordinated, functional disease surveillance systems. The resulting demand for timely information challenges public health leaders to design, develop and implement efficient, flexible and comprehensive systems that integrate staff, resources, and information systems to conduct infectious disease surveillance and response. To understand what resources an integrated disease surveillance and response system would require, we analyzed surveillance requirements for 19 priority infectious diseases targeted for an integrated disease surveillance and response strategy in the WHO African region

Defining the optimal dose of rifapentine for pulmonary tuberculosis: Exposure-response relations from two phase II clinical trials.

Rifapentine is a highly active antituberculosis antibiotic with treatment-shortening potential; however, exposure-response relations and the dose needed for maximal bactericidal activity have not been established. We used pharmacokinetic/pharmacodynamic data from 657 adults with pulmonary tuberculosis participating in treatment trials to compare rifapentine (n = 405) with rifampin (n = 252) as part of intensive-phase therapy. Population pharmacokinetic/pharmacodynamic analyses were performed with nonlinear mixed-effects modeling. Time to stable culture conversion of sputum to negative was determined in cultures obtained over 4 months of therapy. Rifapentine exposures were lower in participants who were coinfected with human immunodeficiency virus, black, male, or fasting when taking drug. Rifapentine exposure, large lung cavity size, and geographic region were independently associated with time to culture conversion in liquid media. Maximal treatment efficacy is likely achieved with rifapentine at 1,200 mg daily. Patients with large lung cavities appear less responsive to treatment, even at high rifapentine doses

Bayesian history matching of complex infectious disease models using emulation: A tutorial and a case study on HIV in Uganda

Advances in scientific computing have allowed the development of complex models that are being routinely applied to problems in disease epidemiology, public health and decision making. The utility of these models depends in part on how well they can reproduce empirical data. However, fitting such models to real world data is greatly hindered both by large numbers of input and output parameters, and by long run times, such that many modelling studies lack a formal calibration methodology. We present a novel method that has the potential to improve the calibration of complex infectious disease models (hereafter called simulators). We present this in the form of a tutorial and a case study where we history match a dynamic, event-driven, individual-based stochastic HIV simulator, using extensive demographic, behavioural and epidemiological data available from Uganda. The tutorial describes history matching and emulation. History matching is an iterative procedure that reduces the simulator's input space by identifying and discarding areas that are unlikely to provide a good match to the empirical data. History matching relies on the computational efficiency of a Bayesian representation of the simulator, known as an emulator. Emulators mimic the simulator's behaviour, but are often several orders of magnitude faster to evaluate. In the case study, we use a 22 input simulator, fitting its 18 outputs simultaneously. After 9 iterations of history matching, a non-implausible region of the simulator input space was identified that was times smaller than the original input space. Simulator evaluations made within this region were found to have a 65% probability of fitting all 18 outputs. History matching and emulation are useful additions to the toolbox of infectious disease modellers. Further research is required to explicitly address the stochastic nature of the simulator as well as to account for correlations between outputs

Efficient History Matching of a High Dimensional Individual-Based HIV Transmission Model

History matching is a model (pre-)calibration method that has been applied to computer models from a wide range of scientific disciplines. In this work we apply history matching to an individual-based epidemiological model of HIV that has 96 input and 50 output parameters, a model of much larger scale than others that have been calibrated before using this or similar methods. Apart from demonstrating that history matching can analyze models of this complexity, a central contribution of this work is that the history match is carried out using linear regression, a statistical tool that is elementary and easier to implement than the Gaussian process--based emulators that have previously been used. Furthermore, we address a practical difficulty with history matching, namely, the sampling of tiny, nonimplausible spaces, by introducing a sampling algorithm adjusted to the specific needs of this method. The effectiveness and simplicity of the history matching method presented here shows that it is a useful tool for the calibration of computationally expensive, high dimensional, individual-based models

Rapid Synthesis of Sub-10 nm Hexagonal NaYF4-Based Upconverting Nanoparticles using Therminol® 66

We report a simple one-pot method for the rapid preparation of sub-10 nm pure hexagonal (β-phase) NaYF4-based upconverting nanoparticles (UCNPs). Using Therminol® 66 as a co-solvent, monodisperse UCNPs could be obtained in unusually short reaction times. By varying the reaction time and reaction temperature, it was possible to control precisely the particle size and crystalline phase of the UCNPs. The upconversion (UC) luminescence properties of the nanocrystals were tuned by varying the concentrations of the dopants (Nd3+ and Yb3+ sensitizer ions and Er3+ activator ions). The size and phase-purity of the as-synthesized core and core–shell nanocrystals were assessed by using complementary transmission electron microscopy, dynamic light scattering, X-ray diffraction, and small-angle X-ray scattering studies. In-depth photophysical evaluation of the UCNPs was pursued by using steady-state and time-resolved luminescence spectroscopy. An enhancement in the UC intensity was observed if the nanocrystals, doped with optimized concentrations of lanthanide sensitizer/activator ions, were further coated with an inert/active shell. This was attributed to the suppression of surface-related luminescence quenching effects

Self-Reported Occupational Exposure to HIV and Factors Influencing its Management Practice: A Study of Healthcare Workers in Tumbi and Dodoma Hospitals, Tanzania.

Blood borne infectious agents such as hepatitis B virus (HBV), hepatitis C virus (HCV) and human immune deficiency virus (HIV) constitute a major occupational hazard for healthcare workers (HCWs). To some degree it is inevitable that HCWs sustain injuries from sharp objects such as needles, scalpels and splintered bone during execution of their duties. However, in Tanzania, there is little or no information on factors that influence the practice of managing occupational exposure to HIV by HCWs. This study was conducted to determine the prevalence of self-reported occupational exposure to HIV among HCWs and explore factors that influence the practice of managing occupational exposure to HIV by HCWs in Tanzania. Self-administered questionnaire was designed to gather information of healthcare workers' occupational exposures in the past 12 months and circumstances in which these injuries occurred. Practice of managing occupational exposure was assessed by the following questions: Nearly half of the HCWs had experienced at least one occupational injury in the past 12 months. Though most of the occupational exposures to HIV were experienced by female nurses, non-medical hospital staff received PEP more frequently than nurses and doctors. Doctors and nurses frequently encountered occupational injuries in surgery room and labor room respectively. HCWs with knowledge on the possibility of HIV transmission and those who knew whom to contact in event of occupational exposure to HIV were less likely to have poor practice of managing occupational exposure. Needle stick injuries and splashes are common among HCWs at Tumbi and Dodoma hospitals. Knowledge of the risk of HIV transmission due to occupational exposure and knowing whom to contact in event of exposure predicted practice of managing the exposure. Thus provision of health education on occupational exposure may strengthen healthcare workers' practices to manage occupational exposure

Investigation on Prevalence of Canine Trypanosomiasis in the Conservation Areas of Bwindi-Mgahinga and Queen Elizabeth in Western Uganda

Nowadays, despite the instauration of several control strategies, animal trypanosomiasis continues to be reported all over Uganda. Few canine African trypanosomiasis (CAT) studies have been carried out, yet dogs are known Trypanosoma reservoirs that share identical home ranges with livestock and serve as parasite link between livestock and humans. This study evaluates the prevalence of CAT in dogs in the Bwindi-Mgahinga and Queen Elizabeth conservation areas. This information will be useful to evaluate the possible role of dogs in the transmission cycle of Trypanosoma species in livestock and wild animals. Trypanosome tests using microhematocrit centrifugation/dark ground microscopy technique (MHCT) followed by conventional polymerase chain reaction (cPCR) were performed in blood samples collected from identified indigenous dogs (n = 124). Four (3.23%) out of 124 dogs were positive for CAT. One dog was positive with Trypanosoma congolense and three with T. vivax. There was no significant statistical difference in CAT prevalence rate in relation to dog's age, sex, and site (P > 0.05). This study reports what we believe is the first time detection of T. congolense and T. vivax in the indigenous dogs found in the Bwindi-Mgahinga and Queen Elizabeth conservation areas in western Uganda. The noticed T. congolense and T. vivax could be responsible for both canine and animal trypanosomiasis and represent a serious threat to the livestock industry. Therefore, there is a need for continuous trypanosomiasis surveillance and integrated management in contiguity to wildlife reserves

Planning an integrated disease surveillance and response system: a matrix of skills and activities

<p>Abstract</p> <p>Background</p> <p>The threat of a global influenza pandemic and the adoption of the World Health Organization (WHO) International Health Regulations (2005) highlight the value of well-coordinated, functional disease surveillance systems. The resulting demand for timely information challenges public health leaders to design, develop and implement efficient, flexible and comprehensive systems that integrate staff, resources, and information systems to conduct infectious disease surveillance and response. To understand what resources an integrated disease surveillance and response system would require, we analyzed surveillance requirements for 19 priority infectious diseases targeted for an integrated disease surveillance and response strategy in the WHO African region.</p> <p>Methods</p> <p>We conducted a systematic task analysis to identify and standardize surveillance objectives, surveillance case definitions, action thresholds, and recommendations for 19 priority infectious diseases. We grouped the findings according to surveillance and response functions and related them to community, health facility, district, national and international levels.</p> <p>Results</p> <p>The outcome of our analysis is a matrix of generic skills and activities essential for an integrated system. We documented how planners used the matrix to assist in finding gaps in current systems, prioritizing plans of action, clarifying indicators for monitoring progress, and developing instructional goals for applied epidemiology and in-service training programs.</p> <p>Conclusion</p> <p>The matrix for Integrated Disease Surveillance and Response (IDSR) in the African region made clear the linkage between public health surveillance functions and participation across all levels of national health systems. The matrix framework is adaptable to requirements for new programs and strategies. This framework makes explicit the essential tasks and activities that are required for strengthening or expanding existing surveillance systems that will be able to adapt to current and emerging public health threats.</p

Phylogenetic Networks and Parameters Inferred from HIV Nucleotide Sequences of High-Risk and General Population Groups in Uganda:Implications for Epidemic Control

Phylogenetic inference is useful in characterising HIV transmission networks and assessing where prevention is likely to have the greatest impact. However, estimating parameters that influence the network structure is still scarce, but important in evaluating determinants of HIV spread. We analyzed 2017 HIV pol sequences (728 Lake Victoria fisherfolk communities (FFCs), 592 female sex workers (FSWs) and 697 general population (GP)) to identify transmission networks on Maximum Likelihood (ML) phylogenetic trees and refined them using time-resolved phylogenies. Network generative models were fitted to the observed degree distributions and network parameters, and corrected Akaike Information Criteria and Bayesian Information Criteria values were estimated. 347 (17.2%) HIV sequences were linked on ML trees (maximum genetic distance ≤4.5%, ≥95% bootstrap support) and, of these, 303 (86.7%) that consisted of pure A1 (n = 168) and D (n = 135) subtypes were analyzed in BEAST v1.8.4. The majority of networks (at least 40%) were found at a time depth of ≤5 years. The waring and yule models fitted best networks of FFCs and FSWs respectively while the negative binomial model fitted best networks in the GP. The network structure in the HIV-hyperendemic FFCs is likely to be scale-free and shaped by preferential attachment, in contrast to the GP. The findings support the targeting of interventions for FFCs in a timely manner for effective epidemic control. Interventions ought to be tailored according to the dynamics of the HIV epidemic in the target population and understanding the network structure is critical in ensuring the success of HIV prevention programs

Leadership in strategic information (LSI) building skilled public health capacity in Ethiopia

<p>Abstract</p> <p>Background</p> <p>In many developing countries, including Ethiopia, few have the skills to use data for effective decision making in public health. To address this need, the U.S. Centers for Disease Control and Prevention (CDC), in collaboration with two local Ethiopian organizations, developed a year long Leadership in Strategic Information (LSI) course to train government employees working in HIV to use data from strategic information sources. A process evaluation of the LSI course examined the impact of the training on trainees' skills and the strengths and weaknesses of the course. The evaluation consisted of surveys and focus groups.</p> <p>Findings</p> <p>Trainees' skill sets increased in descriptive and analytic epidemiology, surveillance, and monitoring and evaluation (M and E). Data from the evaluation indicated that the course structure and the M and E module required revision in order to improve outcomes. Additionally, the first cohort had a high attrition rate. Overall, trainees and key stakeholders viewed LSI as important in building skilled capacity in public health in Ethiopia.</p> <p>Conclusion</p> <p>The evaluation provided constructive insight in modifying the course to improve retention and better address trainees' learning needs. Subsequent course attrition rates decreased as a result of changes made based on evaluation findings.</p