Showing papers by "Pejman Rohani published in 2020"

Transmission dynamics reveal the impracticality of COVID-19 herd immunity strategies.

Abstract: The rapid growth rate of COVID-19 continues to threaten to overwhelm healthcare systems in multiple countries. In response, severely affected countries have had to impose a range of public health strategies achieved via nonpharmaceutical interventions. Broadly, these strategies have fallen into two categories: 1) "mitigation," which aims to achieve herd immunity by allowing the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus to spread through the population while mitigating disease burden, and 2) "suppression," aiming to drastically reduce SARS-CoV-2 transmission rates and halt endogenous transmission in the target population. Using an age-structured transmission model, parameterized to simulate SARS-CoV-2 transmission in the United Kingdom, we assessed the long-term prospects of success using both of these approaches. We simulated a range of different nonpharmaceutical intervention scenarios incorporating social distancing applied to differing age groups. Our modeling confirmed that suppression of SARS-CoV-2 transmission is possible with plausible levels of social distancing over a period of months, consistent with observed trends. Notably, our modeling did not support achieving herd immunity as a practical objective, requiring an unlikely balancing of multiple poorly defined forces. Specifically, we found that 1) social distancing must initially reduce the transmission rate to within a narrow range, 2) to compensate for susceptible depletion, the extent of social distancing must be adaptive over time in a precise yet unfeasible way, and 3) social distancing must be maintained for an extended period to ensure the healthcare system is not overwhelmed.

Nonlinear dynamic analysis of an epidemiological model for COVID-19 including public behavior and government action.

Abstract: This paper is concerned with nonlinear modeling and analysis of the COVID-19 pandemic currently ravaging the planet. There are two objectives: to arrive at an appropriate model that captures the collected data faithfully and to use that as a basis to explore the nonlinear behavior. We use a nonlinear susceptible, exposed, infectious and removed transmission model with added behavioral and government policy dynamics. We develop a genetic algorithm technique to identify key model parameters employing COVID-19 data from South Korea. Stability, bifurcations and dynamic behavior are analyzed. Parametric analysis reveals conditions for sustained epidemic equilibria to occur. This work points to the value of nonlinear dynamic analysis in pandemic modeling and demonstrates the dramatic influence of social and government behavior on disease dynamics.

Detecting critical slowing down in high-dimensional epidemiological systems.

Abstract: Despite medical advances, the emergence and re-emergence of infectious diseases continue to pose a public health threat. Low-dimensional epidemiological models predict that epidemic transitions are preceded by the phenomenon of critical slowing down (CSD). This has raised the possibility of anticipating disease (re-)emergence using CSD-based early-warning signals (EWS), which are statistical moments estimated from time series data. For EWS to be useful at detecting future (re-)emergence, CSD needs to be a generic (model-independent) feature of epidemiological dynamics irrespective of system complexity. Currently, it is unclear whether the predictions of CSD—derived from simple, low-dimensional systems—pertain to real systems, which are high-dimensional. To assess the generality of CSD, we carried out a simulation study of a hierarchy of models, with increasing structural complexity and dimensionality, for a measles-like infectious disease. Our five models included: i) a nonseasonal homogeneous Susceptible-Exposed-Infectious-Recovered (SEIR) model, ii) a homogeneous SEIR model with seasonality in transmission, iii) an age-structured SEIR model, iv) a multiplex network-based model (Mplex) and v) an agent-based simulator (FRED). All models were parameterised to have a herd-immunity immunization threshold of around 90% coverage, and underwent a linear decrease in vaccine uptake, from 92% to 70% over 15 years. We found evidence of CSD prior to disease re-emergence in all models. We also evaluated the performance of seven EWS: the autocorrelation, coefficient of variation, index of dispersion, kurtosis, mean, skewness, variance. Performance was scored using the Area Under the ROC Curve (AUC) statistic. The best performing EWS were the mean and variance, with AUC > 0.75 one year before the estimated transition time. These two, along with the autocorrelation and index of dispersion, are promising candidate EWS for detecting disease emergence.

Transient indicators of tipping points in infectious diseases.

Abstract: The majority of known early warning indicators of critical transitions rely on asymptotic resilience and critical slowing down. In continuous systems, critical slowing down is mathematically described by a decrease in magnitude of the dominant eigenvalue of the Jacobian matrix on the approach to a critical transition. Here, we show that measures of transient dynamics, specifically, reactivity and the maximum of the amplification envelope, also change systematically as a bifurcation is approached in an important class of models for epidemics of infectious diseases. Furthermore, we introduce indicators designed to detect trends in these measures and find that they reliably classify time series of case notifications simulated from stochastic models according to levels of vaccine uptake. Greater attention should be focused on the potential for systems to exhibit transient amplification of perturbations as a critical threshold is approached, and should be considered when searching for generic leading indicators of tipping points. Awareness of this phenomenon will enrich understanding of the dynamics of complex systems on the verge of a critical transition.

Dynamical footprints enable detection of disease emergence

Abstract: Developing methods for anticipating the emergence or reemergence of infectious diseases is both important and timely; however, traditional model-based approaches are stymied by uncertainty surrounding the underlying drivers. Here, we demonstrate an operational, mechanism-agnostic detection algorithm for disease (re-)emergence based on early warning signals (EWSs) derived from the theory of critical slowing down. Specifically, we used computer simulations to train a supervised learning algorithm to detect the dynamical footprints of (re-)emergence present in epidemiological data. Our algorithm was then challenged to forecast the slowly manifesting, spatially replicated reemergence of mumps in England in the mid-2000s and pertussis post-1980 in the United States. Our method successfully anticipated mumps reemergence 4 years in advance, during which time mitigation efforts could have been implemented. From 1980 onwards, our model identified resurgent states with increasing accuracy, leading to reliable classification starting in 1992. Additionally, we successfully applied the detection algorithm to 2 vector-transmitted case studies, namely, outbreaks of dengue serotypes in Puerto Rico and a rapidly unfolding outbreak of plague in 2017 in Madagascar. Taken together, these findings illustrate the power of theoretically informed machine learning techniques to develop early warning systems for the (re-)emergence of infectious diseases.

Nonlinear dynamic analysis of an epidemiological model for COVID-19 including public behavior and government action

Abstract: This paper is concerned with nonlinear modeling and analysis of the COVID-19 pandemic currently ravaging the planet There are two objectives: to arrive at an appropriate model that captures the collected data faithfully, and to use that as a basis to explore the nonlinear behavior We use a nonlinear SEIR (Susceptible, Exposed, Infectious & Removed) transmission model with added behavioral and government policy dynamics We develop a genetic algorithm technique to identify key model parameters employing COVID19 data from South Korea Stability, bifurcations and dynamic behavior are analyzed Parametric analysis reveals conditions for sustained epidemic equilibria to occur This work points to the value of nonlinear dynamic analysis in pandemic modeling and demonstrates the dramatic influence of social and government behavior on disease dynamics

Overcoming Waning Immunity in Pertussis Vaccines: Workshop of the National Institute of Allergy and Infectious Diseases

Abstract: Despite high vaccine coverage in many parts of the world, pertussis is resurging in a number of areas in which acellular vaccines are the primary vaccine administered to infants and young children. This is attributed in part to the suboptimal and short-lived immunity elicited by acellular pertussis vaccines and to their inability to prevent nasal colonization and transmission of the etiologic agent Bordetella pertussis In response to this escalating public health concern, the National Institute of Allergy and Infectious Diseases held the workshop "Overcoming Waning Immunity in Pertussis Vaccines" in September 2019 to identify issues and possible solutions for the defects in immunity stimulated by acellular pertussis vaccines. Discussions covered aspects of the current problem, gaps in knowledge and possible paths forward. This review summarizes presentations and discussions of some of the key points that were raised by the workshop.

The First Report of Differences in Gut Microbiota Composition between Obese and Normal Weight Iranian Subjects

Abstract: Background OObesity is a complex disorder influenced by various genetic and environmental factors. It has been shown that gut microbiota, which colonizes gastrointestinal tract, has a substantial role as an environmental factor in the pathophysiology of obesity. Since the composition of gut microbiota alters with regard to different criteria, such as ethnicity, geographical location, diet, lifestyle, age, and gender, we aimed to determine firmicutes/bacteroidetes (F/B) ratio and the abundance of important gut microbiota members, Akkermansia muciniphila, Faecalibacterium prausnitzii, Roseburia, Bifidobacterium, and Prevotella in Iranian obese and normal weight individuals, for the first time. Methods In this study, 50 normal and 50 obese subjects were recruited and classified based on their BMI into normal weight and obese groups. Stool samples were collected. Following DNA extraction from the samples, quantitative PCR was conducted based on 16s rDNA universal primers. Finally, the correlation between the bacterial abundance and obesity was analyzed by statistical analyses. Results We observed a significant increase of F/B ratio in the obese group, compared to the normal weight group (p = 0.002). Although A. muciniphila (p = 0.039) and Bifidobacterium (p = 0.049) abundance significantly decreased, the abundance of F. prausnitzii (p = 0.046) significantly elevated with BMI increase in the studied groups. Conclusion Owing to the importance of the gut microbiota composition in obesity development, determination and targeted restoration of gut microbiota pattern could be valuable in the control and treatment of obesity in certain populations.

COVID-19 herd immunity strategies: walking an elusive and dangerous tightrope

Abstract: The rapid growth in cases of COVID-19 has threatened to overwhelm healthcare systems in multiple countries. In response, severely affected countries have had to consider a range of public health strategies achieved by implementing non-pharmaceutical interventions. Broadly, these strategies have fallen into two categories: i) "mitigation", which aims to achieve herd immunity by allowing the SARS-CoV-2 virus to spread through the population while mitigating disease burden, and ii) "suppression", aiming to drastically reduce SARS-CoV-2 transmission rates and halt endogenous transmission in the target population. Using an age-structured transmission model, parameterised to simulate SARS-CoV-2 transmission in the UK, we assessed the prospects of success using both of these approaches. We simulated a range of different non-pharmaceutical intervention scenarios incorporating social distancing applied to differing age groups. We found that it is possible to suppress SARS-CoV-2 transmission if social distancing measures are sustained at a sufficient level for a period of months. Our modelling did not support achieving herd immunity as a practical objective, requiring an unlikely balancing of multiple poorly-defined forces. Specifically, we found that: i) social distancing must initially reduce the transmission rate to within a narrow range, ii) to compensate for susceptible depletion, the extent of social distancing must be vary over time in a precise but unfeasible way, and iii) social distancing must be maintained for a long duration (over 6 months).

Persistent elevation of aspartate aminotransferase in a child after incomplete Kawasaki disease: a case report and literature review

Abstract: Interpretation of abnormalities in liver function tests, especially in asymptomatic children, is a common problem faced by clinicians. Isolated elevation of aspartate aminotransferase may further puzzle physicians. Macro-aspartate aminotransferase (AST) results from complexes AST produces with other plasma components, such as immunoglobulin. To our knowledge, this is the first report on a case of macro-AST-associated incomplete Kawasaki disease (KD). It is to make physicians aware of this benign condition and help to prevent extensive, unnecessary investigations and invasive workups. A 16-month old boy with a 7-day history of fever was admitted to our pediatric ward for pyrexia workup. After complete investigations, KD was confirmed by a pediatric rheumatologist. During his admission and serial follow-up tests, an isolated AST elevation was noted. Comprehensive tests were performed and using the polyethylene glycol (PEG) precipitation method, macro-AST was confirmed. The patient has been followed up for 3 years, and so far, the benign nature of this condition has been confirmed. Clinicians should consider testing for macro-AST when elevated AST is the only abnormal lab finding. Although an uncommon finding, macro-AST may be seen in both children and adults. There are many reasons for this phenomenon, including resolved acute hepatitis or in some cases, inflammatory bowel disease, hepatic malignancy, monoclonal gammapathy, celiac disease, or KD; however, it may be observed in asymptomatic healthy children as well. Using the PEG precipitation method, a definitive diagnosis can be made. In none of these conditions does macro-AST have any prognostic significance. An appreciation of macro-AST may prevent the need for more invasive investigations to which patients may be unnecessarily subjected. It is important to recognize this condition as benign and assure patients that no specific treatment is required.

Implementation and adherence of routine pertussis vaccination (DTP) in a low-resource urban birth cohort

Abstract: Introduction Reliable information on rates of up-to-date coverage and timely administration of routine childhood immunisations are critical for guiding public health efforts worldwide, yet prospective observation of vaccination programmes within individual communities is rare. Here, we provide a longitudinal analysis of the directly observed administration of a three-dose primary vaccination series to infants in a low-resource community in Lusaka, Zambia. Methods Throughout 2015, we recruited a longitudinal birth cohort of mother/infant pairs (initial enrolment, 1981 pairs; attending, 1497 pairs) from the periurban informal settlement of Chawama compound, located in Lusaka, Zambia. We prospectively monitored the administration of scheduled diphtheria–tetanus–pertussis (DTP) vaccinations across the first 14–18 weeks of life. We analysed study attendance and vaccine coverage, both overall and stratified by age group. We employed Kaplan-Meier analyses to estimate delays in age-appropriate administration of vaccine doses. We also assessed schedule timing violations, including early and compressed dose administration. Results At study completion, first dose (DTP1) rates were high (92.9% of attending), whereas third dose completion (DTP3) rates were far lower (61.9%). Missed vaccinations and study dropout both contributed to the low DTP3 completion rates. DTP1 was administered very late (at or after 10 weeks) to 61 infants (4.1%). DTP1 was administered too early to 64 infants (4.3%), and 77 (5.1%) received consecutive doses below the minimum recommended spacing of 28 days. Conclusions We observe substantial individual variation in the timing of early childhood DTP doses, though following this birth cohort proved challenging. Our results indicate that timely administration of both DTP1 and DTP3 remains a challenge in this community. These directly-observed, individual-based results provide an important counterpoint to more course-grained, survey-based national and province estimates of up-to-date vaccine coverage. This study also highlights the challenges of vaccine hesitancy and suboptimal utilisation of (no-cost) healthcare services in a low-resource urban setting.

Coronavirus disease 2019 (COVID-19) and pediatric gastroenterology.

Abstract: The coronavirus disease 2019 (COVID-19) is responsible for the new pandemic, which remains an important health and economic challenge worldwide. The causative agent is a novel coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is similar to SARS-CoV-1 and Middle East respiratory syndrome coronavirus (MERS-CoV). Adult infection with respiratory symptoms was considered in the beginning of the pandemic. Now, it has been reported that SARS-CoV-2 infects children and other organs such as the gastrointestinal tract. SARS-CoV-2 enters the host cells through angiotensin converting enzyme-2 (ACE2) receptors as the main receptor expressed in various organs such as the lungs and gastrointestinal tract. Studies on children and the clinical manifestations of COVID-19 do not completely explain the natural course of infection in children, and precisely how the GI tract is involved is not understood. The present article highlights the gastrointestinal manifestations and pathological findings in children with COVID-19. According to the evidence, SARS-CoV-2 infection is milder in children and may present different clinical symptoms from adults. Common clinical manifestations of pediatric COVID-19 include cough, fever, sore throat, malaise, fatigue, and GI symptoms such as diarrhea, abdominal pain, nausea, and vomiting. Furthermore, liver and pancreatic enzymes may be elevated during the pediatric COVID-19 course. Asymptomatic children carriers are potential sources of infection for adults, especially elderly ones. Diagnosis, treatment, and isolation of children are the most effective ways to control the expansion of the COVID-19 pandemic.

Alternative stable states, tipping points, and early warning signals of ecological transitions

Abstract: Ecological systems are prone to dramatic shifts between alternative stable states. In reality, these shifts are often caused by slow forces external to the system that eventually push it over a tipping point. Theory predicts that when ecological systems are brought close to a tipping point, the dynamical feedback intrinsic to the system interact with intrinsic noise and extrinsic perturbations in characteristic ways. The resulting phenomena thus serve as “early warning signals” for shifts such as population collapse. In this chapter, we review the basic (qualitative) theory of such systems. We then illustrate the main ideas with a series of models that both represent fundamental ecological ideas (e.g. density-dependence) and are amenable to mathematical analysis. These analyses provide theoretical predictions about the nature of measurable fluctuations in the vicinity of a tipping point. We conclude with a review of empirical evidence from laboratory microcosms, field manipulations, and observational studies.

The Effect of Nutritional Consultation on the Level of Malnutrition and Growth Indices in Children with Cystic Fibrosis

Abstract: Background: Malnutrition is one of the most common disorders among children with Cystic Fibrosis (CF). The present study aimed to investigate the effect of nutritional consultation on the type and severity of malnutrition in children with CF. Materials and Methods: This quasi-experimental study was conducted on 78 children with CF referred to Mofid Pediatric Hospital, Tehran, Iran, in 2017-2018. Their parents filled the demographic questionnaire. Participants with malnutrition were undergoing the assessment on growth indices, including weight, height, ideal body weight, mid-upper arm circumference, and Z-score. Moreover, the nutritional consultations were considered for them (30-45 minutes). Children and their parents were consulted and trained about total daily calorie acquirement, type, number of the meal, amount of food intake, drinks, and avoided eating of any low-calorie food like snacks, during the consultation. All patients were reassessed three months later for growth indices. The data were analyzed using SPSS software version 22.0. Results: We assessed 78 children with CF, 21 (26%) of them had mild, 26 (34%) moderate malnutrition, and 31 (40%) severe malnutrition. The result showed that nutritional intervention was effective. Consequently, 1 (3.8%) of the moderately malnourished child was improved to mild malnutrition and 5 (27.8%) children under five years old were improved from severe to moderate malnutrition. Moreover, 1 (5.6%) child were improved from severe to mild, and 2 (15.4%) of children over five years old were improved from severe to moderate malnutrition. Conclusion: According to the results, the early growth assessment in hospitalized and outpatient, diagnosis of malnutrition and nutritional interventionwill be useful in improving the severity of malnutrition and growth indices in children with CF.

Asymptomatic Bordetella pertussis infections in young African infants and their mothers identified within a longitudinal cohort

Abstract: Despite long-standing vaccination programs, pertussis incidence has increased in numerous countries; transmission by asymptomatic individuals is a suspected driver of this resurgence. However, unequivocal evidence documenting asymptomatic infections in adults and children is lacking due, in part, to the cross-sectional nature of most pertussis surveillance studies. In addition, modern pertussis surveillance relies on quantitative PCR (qPCR) using fixed diagnostic thresholds to identify cases. To address this gap, we present a longitudinal analysis of 17,442 nasopharyngeal samples collected from a cohort of 1,320 Zambian mother/infant pairs. Using full-range cycle threshold (CT) values from IS481 qPCR assays, we document widespread asymptomatic infections among mothers and also, surprisingly, among young infants. From an initial group of eight symptomatic infants who tested positive by qPCR, we identify frequent contemporaneous subclinical infections in mothers. Within the full cohort, we observe strong temporal correlation between low- and high-intensity qPCR signals. We compute a single time-averaged score for each individual summarizing the evidence for pertussis infection (EFI), and show that EFI strongly clusters within mother/infant pairs, and is strongly associated with clinical symptomatology and antibiotic use. Overall, the burden of pertussis here is substantially underestimated when restricting diagnostic criteria to IS481 CT≤35. Rather, we find that full-range CT values provide valuable insights into pertussis epidemiology in this population, and illuminate the infection arc within individuals. These findings have significant implications for quantifying asymptomatic pertussis prevalence and its contribution to overall transmission. Our results also expose limitations of threshold-based interpretations of qPCR assays in infectious disease surveillance. IMPORTANCE STATEMENT Current pertussis epidemiology rests largely on cross-sectional surveys that use diagnostic thresholds to interpret qPCR results as positive or negative, and thus fail to capture arcs of infection within individuals or populations. By longitudinally monitoring a cohort of African mother/infant pairs and using full-range qPCR results, we quantify the otherwise-hidden evidence for pertussis infection (EFI) in individuals. We demonstrate strong clustering of EFI within mother/infant pairs and quantify the association between EFI and both pertussis symptoms and antibiotic use. Critically, we find strong evidence that asymptomatic pertussis is common in both infants and mothers, indicating that the burden of pertussis has been significantly underestimated in this population. Our results also inform qPCR-based monitoring of other pathogens, such as SARS-CoV-2.

Five approaches to the suppression of SARS-CoV-2 without intensive social distancing

Abstract: Initial efforts to mitigate transmission of SARS-CoV-2 relied on intensive social distancing measures such as school and workplace closures, shelter-in-place orders, and prohibitions on the gathering of people. Other non-pharmaceutical interventions for suppressing transmission include active case finding, contact tracing, quarantine, immunity or health certification, and a wide range of personal protective measures. Here we investigate the potential effectiveness of these alternative approaches to suppression. We introduce a conceptual framework represented by two mathematical models that differ in strategy. We find both strategies may be effective, although both require extensive testing and work within a relatively narrow range of conditions. Generalized protective measures such as wearing face masks, improved hygiene, and local reductions in density are found to significantly increase the effectiveness of targeted interventions.

Does Celiac Disease Affect Antibody Production Against Hepatitis B in Children

Abstract: Background: Celiac disease is an immune-mediated systemic disease, in which gluten ingestion causes different symptoms. HLA-DQ2 is positive in 90% - 95% of celiac patients. HLA has been considered to inhibit antibody production against the hepatitis B virus vaccine. Considering that celiac disease affects about 1% of the population, this phenomenon could be a significant factor in immunization programs. On the other hand, HLA-DQ2 positive patients not only are at the risk of HBV infection themselves but also have the potential to be an important source of HBV dissemination in the world. Objectives: This study was carried out to evaluate the responsiveness of celiac-affected children to HBV vaccination in Iran. Methods: This case-control prospective study was performed on 62 Iranian children (31 children with confirmed celiac disease before introducing a gluten-free diet and 31 healthy children). HBS Ab (antibody against hepatitis B virus surface antigen) titer was checked in the patients and compared between the two groups. Results: It was shown that 67.7% of cases and 64.5% of controls had HBS Ab titer above 10 mIU/mL, but the difference was not significant statistically. After matching for the time interval from the last HBV vaccination, it was observed that although non-significantly, celiac disease can decrease the chance for anti-HBS production up to 30%. Conclusions: This study did not confirm non-responsiveness against the HBV vaccine in celiac disease in children. This may be due to genetic factors or type of vaccine. Moreover, in our study, responsiveness was assessed qualitatively in the two groups (HBS Ab > 10 mIU/mL was considered as a responder).

Assessment of validity and reliability of the NutriCHEQ Questionnaire for identifying children aged 1 to 3 years at nutritional risk

Abstract: Assessment of validity and reliability of the NutriCHEQ Questionnaire for identifying children aged 1 to 3 years at nutritional risk