Accounting for Underreporting in Mathematical Modeling of Transmission and Control of COVID-19 in Iran

Iran has been the country most affected by the outbreak of SARS-CoV-2 in the Middle East. With a relatively high case fatality ratio and limited testing capacity, the number of confirmed cases reported is suspected to suffer from significant underreporting. Therefore, understanding the transmission dynamics of COVID-19 and assessing the effectiveness of the interventions that have taken place in Iran while accounting for the uncertain level of underreporting is of critical importance. In this paper, we developed a compartmental transmission model to estimate the time-dependent effective reproduction number since the beginning of the outbreak in Iran. We associate the variations in the effective reproduction number with a timeline of interventions and national events. The estimation method accounts for the underreporting due to low case ascertainment. Our estimates of the effective reproduction number ranged from 0.66 to 1.73 between February and April 2020, with a median of 1.16. We estimate a reduction in the effective reproduction number during this period, from 1.73 (95% CI 1.60–1.87) on 1 March 2020 to 0.69 (95% CI 0.68–0.70) on 15 April 2020, due to various non-pharmaceutical interventions. The series of non-pharmaceutical interventions and the public compliance that took place in Iran are found to be effective in slowing down the speed of the spread of COVID-19. However, we argue that if the impact of underreporting is overlooked, the estimated transmission and control dynamics could mislead public health decisions, policy makers, and the general public

Accounting for Underreporting in Mathematical Modeling of Transmission and Control of COVID-19 in Iran

Iran has been the country most affected by the outbreak of SARS-CoV-2 in the Middle East. With a relatively high case fatality ratio and limited testing capacity, the number of confirmed cases reported is suspected to suffer from significant underreporting. Therefore, understanding the transmission dynamics of COVID-19 and assessing the effectiveness of the interventions that have taken place in Iran while accounting for the uncertain level of underreporting is of critical importance. In this paper, we developed a compartmental transmission model to estimate the time-dependent effective reproduction number since the beginning of the outbreak in Iran. We associate the variations in the effective reproduction number with a timeline of interventions and national events. The estimation method accounts for the underreporting due to low case ascertainment. Our estimates of the effective reproduction number ranged from 0.66 to 1.73 between February and April 2020, with a median of 1.16. We estimate a reduction in the effective reproduction number during this period, from 1.73 (95% CI 1.60–1.87) on 1 March 2020 to 0.69 (95% CI 0.68–0.70) on 15 April 2020, due to various non-pharmaceutical interventions. The series of non-pharmaceutical interventions and the public compliance that took place in Iran are found to be effective in slowing down the speed of the spread of COVID-19. However, we argue that if the impact of underreporting is overlooked, the estimated transmission and control dynamics could mislead public health decisions, policy makers, and the general public

Survey of prenatal screening policies in Europe for structural malformations and chromosome anomalies, and their impact on detection and termination rates for neural tube defects and Down's syndrome

OBJECTIVE: To 'map' the current (2004) state of prenatal screening in Europe. DESIGN: (i) Survey of country policies and (ii) analysis of data from EUROCAT (European Surveillance of Congenital Anomalies) population-based congenital anomaly registers. SETTING: Europe. POPULATION: Survey of prenatal screening policies in 18 countries and 1.13 million births in 12 countries in 2002-04. METHODS: (i) Questionnaire on national screening policies and termination of pregnancy for fetal anomaly (TOPFA) laws in 2004. (ii) Analysis of data on prenatal detection and termination for Down's syndrome and neural tube defects (NTDs) using the EUROCAT database. MAIN OUTCOME MEASURES: Existence of national prenatal screening policies, legal gestation limit for TOPFA, prenatal detection and termination rates for Down's syndrome and NTD. RESULTS: Ten of the 18 countries had a national country-wide policy for Down's syndrome screening and 14/18 for structural anomaly scanning. Sixty-eight percent of Down's syndrome cases (range 0-95%) were detected prenatally, of which 88% resulted in termination of pregnancy. Eighty-eight percent (range 25-94%) of cases of NTD were prenatally detected, of which 88% resulted in termination. Countries with a first-trimester screening policy had the highest proportion of prenatally diagnosed Down's syndrome cases. Countries with no official national Down's syndrome screening or structural anomaly scan policy had the lowest proportion of prenatally diagnosed Down's syndrome and NTD cases. Six of the 18 countries had a legal gestational age limit for TOPFA, and in two countries, termination of pregnancy was illegal at any gestation. CONCLUSIONS: There are large differences in screening policies between countries in Europe. These, as well as organisational and cultural factors, are associated with wide country variation in prenatal detection rates for Down's syndrome and NTD

Health behaviour modelling for prenatal diagnosis in Australia: a geodemographic framework for health service utilisation and policy development

BACKGROUND: Despite the wide availability of prenatal screening and diagnosis, a number of studies have reported no decrease in the rate of babies born with Down syndrome. The objective of this study was to investigate the geodemographic characteristics of women who have prenatal diagnosis in Victoria, Australia, by applying a novel consumer behaviour modelling technique in the analysis of health data. METHODS: A descriptive analysis of data on all prenatal diagnostic tests, births (1998 and 2002) and births of babies with Down syndrome (1998 to 2002) was undertaken using a Geographic Information System and socioeconomic lifestyle segmentation classifications. RESULTS: Most metropolitan women in Victoria have average or above State average levels of uptake of prenatal diagnosis. Inner city women residing in high socioeconomic lifestyle segments who have high rates of prenatal diagnosis spend 20% more on specialist physician's fees when compared to those whose rates are average. Rates of prenatal diagnosis are generally low amongst women in rural Victoria, with the lowest rates observed in farming districts. Reasons for this are likely to be a combination of lack of access to services (remoteness) and individual opportunity (lack of transportation, low levels of support and income). However, there are additional reasons for low uptake rates in farming areas that could not be explained by the behaviour modelling. These may relate to women's attitudes and choices. CONCLUSION: A lack of statewide geodemographic consistency in uptake of prenatal diagnosis implies that there is a need to target health professionals and pregnant women in specific areas to ensure there is increased equity of access to services and that all pregnant women can make informed choices that are best for them. Equally as important is appropriate health service provision for families of children with Down syndrome. Our findings show that these potential interventions are particularly relevant in rural areas. Classifying data to lifestyle segments allowed for practical comparisons of the geodemographic characteristics of women having prenatal diagnosis in Australia at a population level. This methodology may in future be a feasible and cost-effective tool for service planners and policy developers

Plasma metabolomics of presymptomatic PSEN1-H163Y mutation carriers: a pilot study

Background and Objective: PSEN1-H163Y carriers, at the presymptomatic stage, have reduced 18FDG-PET binding in the cerebrum of the brain (Scholl et al., Neurobiol Aging 32:1388–1399, 2011). This could imply dysfunctional energy metabolism in the brain. In this study, plasma of presymptomatic PSEN1 mutation carriers was analyzed to understand associated metabolic changes. Methods: We analyzed plasma from noncarriers (NC, n = 8) and presymptomatic PSEN1-H163Y mutation carriers (MC, n = 6) via untargeted metabolomics using gas and liquid chromatography coupled with mass spectrometry, which identified 1199 metabolites. All the metabolites were compared between MC and NC using univariate analysis, as well as correlated with the ratio of Ab1–42/Ab1–40, using Spearman’s correlation. Altered metabolites were subjected to Ingenuity Pathway Analysis (IPA). Results: Based on principal component analysis the plasma metabolite profiles were divided into dataset A and dataset B. In dataset A, when comparing between presymptomatic MC and NC, the levels of 79 different metabolites were altered. Out of 79, only 14 were annotated metabolites. In dataset B, 37 metabolites were significantly altered between presymptomatic MC and NC and nine metabolites were annotated. In both datasets, annotated metabolites represent amino acids, fatty acyls, bile acids, hexoses, purine nucleosides, carboxylic acids, and glycerophosphatidylcholine species. 1-docosapentaenoyl-GPC was positively correlated, uric acid and glucose were negatively correlated with the ratio of plasma Ab1–42/Ab1–40 (P < 0.05). Interpretation: This study finds dysregulated metabolite classes, which are changed before the disease symptom onset. Also, it provides an opportunity to compare with sporadic Alzheimer’s Disease. Observed findings in this study need to be validated in a larger and independent Familial Alzheimer’s Disease (FAD) cohort

Methods to estimate access to care and the effect of interventions on the outcomes of congenital disorders

In the absence of intervention, early-onset congenital disorders lead to pregnancy loss, early death, or disability. Currently, lack of epidemiological data from many settings limits the understanding of the burden of these conditions, thus impeding health planning, policy-making, and commensurate resource allocation. The Modell Global Database of Congenital Disorders (MGDb) seeks to meet this need by combining general biological principles with observational and demographic data, to generate estimates of the burden of congenital disorders. A range of interventions along the life course can modify adverse outcomes associated with congenital disorders. Hence, access to and quality of services available for the prevention and care of congenital disorders affects both their birth prevalence and the outcomes for affected individuals. Information on this is therefore important to enable burden estimates for settings with limited observational data, but is lacking from many settings. This paper, the third in this special issue on methods used in the MGDb for estimating the global burden of congenital disorders, describes key interventions that impact on outcomes of congenital disorders and methods used to estimate their coverage where empirical data are not available

Atrioventricular septal defects among infants in Europe: a population-based study of prevalence, associated anomalies, and survival.

OBJECTIVE: To describe the epidemiology of chromosomal and non-chromosomal cases of atrioventricular septal defects in Europe. METHODS: Data were obtained from EUROCAT, a European network of population-based registries collecting data on congenital anomalies. Data from 13 registries for the period 2000-2008 were included. RESULTS: There was a total of 993 cases of atrioventricular septal defects, with a total prevalence of 5.3 per 10,000 births (95% confidence interval 4.1 to 6.5). Of the total cases, 250 were isolated cardiac lesions, 583 were chromosomal cases, 79 had multiple anomalies, 58 had heterotaxia sequence, and 23 had a monogenic syndrome. The total prevalence of chromosomal cases was 3.1 per 10,000 (95% confidence interval 1.9 to 4.3), with a large variation between registers. Of the 993 cases, 639 cases were live births, 45 were stillbirths, and 309 were terminations of pregnancy owing to foetal anomaly. Among the groups, additional associated cardiac anomalies were most frequent in heterotaxia cases (38%) and least frequent in chromosomal cases (8%). Coarctation of the aorta was the most common associated cardiac defect. The 1-week survival rate for live births was 94%. CONCLUSION: Of all cases, three-quarters were associated with other anomalies, both chromosomal and non-chromosomal. For infants with atrioventricular septal defects and no chromosomal anomalies, cardiac defects were often more complex compared with infants with atrioventricular septal defects and a chromosomal anomaly. Clinical outcomes for atrioventricular septal defects varied between regions. The proportion of termination of pregnancy for foetal anomaly was higher for cases with multiple anomalies, chromosomal anomalies, and heterotaxia sequence

Estimating the birth prevalence and pregnancy outcomes of congenital malformations worldwide

Congenital anomaly registries have two main surveillance aims: firstly to define baseline epidemiology of important congenital anomalies to facilitate programme, policy and resource planning, and secondly to identify clusters of cases and any other epidemiological changes that could give early warning of environmental or infectious hazards. However, setting up a sustainable registry and surveillance system is resource-intensive requiring national infrastructure for recording all cases and diagnostic facilities to identify those malformations that that are not externally visible. Consequently, not all countries have yet established robust surveillance systems. For these countries, methods are needed to generate estimates of prevalence of these disorders which can act as a starting point for assessing disease burden and service implications. Here, we describe how registry data from high-income settings can be used for generating reference rates that can be used as provisional estimates for countries with little or no observational data on non-syndromic congenital malformations

Prevalence of Esophageal Atresia among 18 International Birth Defects Surveillance Programs

BACKGROUND: The prevalence of esophageal atresia (EA) has been shown to vary across different geographical settings. Investigation of geographical differences may provide an insight into the underlying etiology of EA. METHODS: The study population comprised infants diagnosed with EA during 1998 to 2007 from 18 of the 46 birth defects surveillance programs, members of the International Clearinghouse for Birth Defects Surveillance and Research. Total prevalence per 10,000 births for EA was defined as the total number of cases in live births, stillbirths, and elective termination of pregnancy for fetal anomaly (ETOPFA) divided by the total number of all births in the population. RESULTS: Among the participating programs, a total of 2943 cases of EA were diagnosed with an average prevalence of 2.44 (95% confidence interval [CI], 2.352.53) per 10,000 births, ranging between 1.77 and 3.68 per 10,000 births. Of all infants diagnosed with EA, 2761 (93.8%) were live births, 82 (2.8%) stillbirths, 89 (3.0%) ETOPFA, and 11 (0.4%) had unknown outcomes. The majority of cases (2020, 68.6%), had a reported EA with fistula, 749 (25.5%) were without fistula, and 174 (5.9%) were registered with an unspecified code. CONCLUSIONS: On average, EA affected 1 in 4099 births (95% CI, 1 in 39544251 births) with prevalence varying across different geographical settings, but relatively consistent over time and comparable between surveillance programs. Findings suggest that differences in the prevalence observed among programs are likely to be attributable to variability in population ethnic compositions or issues in reporting or registration procedures of EA, rather than a real risk occurrence difference. Birth Defects Research (Part A), 2012. (c) 2012 Wiley Periodicals, Inc