Disease Burden of 32 Infectious Diseases in the Netherlands, 2007-2011

BackgroundInfectious disease burden estimates provided by a composite health measure give a balanced view of the true impact of a disease on a population, allowing the relative impact of diseases that differ in severity and mortality to be monitored over time. This article presents the first national disease burden estimates for a comprehensive set of 32 infectious diseases in the Netherlands.ConclusionsFor guiding and supporting public health policy decisions regarding the prioritisation of interventions and preventive measures, estimates of disease burden and the comparison of burden between diseases can be informative. Although the collection of disease-specific parameters and estimation of incidence is a process subject to continuous improvement, the current study established a baseline for assessing the impact of future public health initiatives.     

Maternal and Antenatal Risk Factors for Stillbirths and Neonatal Mortality in Rural Bangladesh: A Case-Control Study

Objective

To identify maternal and antenatal factors associated with stillbirths and neonatal deaths in rural Bangladesh.

Study Design

A prospective cohort study is being conducted to evaluate a maternal and child nutrition program in rural Bangladesh. Cases were all stillbirths and neonatal deaths that occurred in the cohort between March 7, 2011 and December 30, 2011. Verbal autopsies were used to determine cause of death. For each case, four controls were randomly selected from cohort members alive at age 3-months. Multivariable logistic regression was used to identify factors associated with these deaths.

Results

Overall, 112 adverse pregnancy outcomes (44 stillbirths, 19/1,000 births; 68 neonatal deaths, 29/1,000 live births) were reported. Of the stillbirths 25 (56.8%) were fresh. The main causes of neonatal death were birth asphyxia (35%), sepsis (28%) and preterm birth (19%). History of bleeding during pregnancy was the strongest risk factor for stillbirths (adjusted odds ratio 22.4 [95% confidence interval 2.5, 197.5]) and neonatal deaths (adjusted odds ratio 19.6 [95% confidence interval 2.1, 178.8]). Adequate maternal nutrition was associated with decreased risk of neonatal death (adjusted odds ratio 0.4 [95% confidence interval 0.2, 0.8]).

Conclusions

Identifying high-risk pregnancies during gestation and ensuring adequate antenatal and obstetric care needs to be a priority for any community-based maternal and child health program in similar settings.     

Perinatal mortality: a continuing collaborative regional survey.

A collaborative survey of perinatal mortality in each district of the Northern region set up in July 1980 was able to obtain information on 99% of all the registered perinatal deaths among babies born in 1981-2 to mothers resident in the region. There were 12.4 perinatal deaths/1000 births over this two year period, but 41% of the stillbirths and early neonatal deaths were of babies with a lethal malformation or weighing less than 1000 g at birth (or both). All causes of perinatal mortality had become less common than they had been at the time of the National Birthday Trust survey in 1958, though there had been a relatively small decrease in the number of deaths due to malformation (in the absence of any neural tube defect) and in the number of stillbirths of normally developed fetuses: 36% of the antepartum stillbirths among non-malformed singleton fetuses were associated with poor fetal growth (weight below the fifth centile at birth) and 21% were due to sudden unexplained placental abruption.     

The influence of antenatal and maternal factors on stillbirths and neonatal deaths in New South Wales, Australia

This study identified the influences of maternal socio-demographic and antenatal factors on stillbirths and neonatal deaths in New South Wales, Australia. Bivariate and multivariate analyses were used to explore the association of selected antenatal and maternal characteristics with stillbirths and neonatal deaths. The findings of this study showed that stillbirths and neonatal deaths significantly varied by infant sex, maternal age, Aboriginality, maternal country of birth, socioeconomic status, parity, maternal smoking behaviour during pregnancy, maternal diabetes mellitus, maternal hypertension, antenatal care, plurality of birth, low birth weight, place of birth, delivery type, maternal deaths and small gestational age. First-born infants, twins and infants born to teenage mothers, Aboriginal mothers, those who smoked during the pregnancy and those of lower socioeconomic status were at increased risk of stillbirths and neonatal deaths. The most common causes of stillbirths were conditions originating in the perinatal period: intrauterine hypoxia and asphyxia. Congenital malformations, including deformities and chromosomal abnormalities, and disorders related to slow fetal growth, short gestation and low birth weight were the most common causes of neonatal deaths. The findings indicate that very low birth weight (less than 2,000 g) contributed 75.6% of the population-attributable risks to stillbirths and 59.4% to neonatal deaths. Low gestational age (less than 32 weeks) accounted for 77.7% of stillbirths and 87.9% of neonatal deaths. The findings of this study suggest that in order to reduce stillbirths and neonatal deaths, it is essential to include strategies to predict and prevent prematurity and low birth weight, and that there is a need to focus on anti-smoking campaigns during pregnancy, optimizing antenatal care and other healthcare programmes targeted at the socially disadvantaged populations identified in this study.     

Pregnancy wastage and age of mother among the Amish

Reports of approximately 7500 pregnancies in reproductive histories collected by Colette Wiffler through personal interviews with Old Order Amish families of Illinois, Iowa, Missouri, and Wisconsin during the 1968 through 1973 period were analyzed to test a prediction: a society in which healthy women generally want large numbers of children and do not marry unusually uoung should exhibit a slower rate of increase in fetal death ratios with age of mother than the general US population. In this study, fetal deaths occurring after 7 months of gestation were called stillbirths; those occurring between 6 weeks and 7 months were termed miscarriages. Neonatal deaths occurred within the 1st week following live birth. All loss ratios were calculated as the number of the specified type of pregnancy loss/1000 pregnancies which lasted at least 7 months. The minimum miscarriage and stillbirth ratios each occurred in the early 30s, but the ratios were not statistically different from those for mothers in their early 20s. The interpretation of the observation is complicated by substantial reductions in pregnancy wastage experienced by the general population over the long span of time (1898 through 1972) covered by the present data. For the US both late fetal death ratios and neonatal death rates specific for the age of the mother reach their minimum in the early 20s. While most available data provide information about late fetal death only, the study of pregnancies in New York's Health Insurance Plan revealed markedly higher fetal death ratios for mothers in the early 30s than for mothers in their 20s both for gestations of 12-19 weeks and for those of less than 12 weeks. Thus, the Amish fetal deaths differ from the general US pattern similarly for miscarriages and for the less numerous stillbirths. These results are compatible with the prediction under test but conflict with the expectations of the traditional idea that women in their early 20s have their ability to carry pregnancies to live birth impaired by age. The findings suggest that any increase in risk of fetal death caused by increasing age of an individual mother must be unimportant before age 35. It appears that women who decide to postpone their pregnancies until their late 20s or early 30s are probably not materially increasing the risk of fetal death. The same appears to be the case for early infant mortality.     

Modeling the potential public health impact of prepregnancy obesity on adverse fetal and infant outcomes

Objective: Approximately one‐third of US reproductive‐aged women are obese, and prepregnancy obesity is a strong risk factor for adverse fetal and infant outcomes. The annual number of preventable adverse fetal and infant outcomes associated with prepregnancy obesity in the US was estimated. Design and Methods: Adverse fetal and infant outcomes for which statistically significant associations with prepregnancy obesity had been reported by peer‐reviewed meta‐analyses, which included fetal deaths and nine different major birth defects, were assessed. The true prevalence of prepregnancy obesity was estimated by multiplying self‐reported prepregnancy obesity by a bias factor based on the difference between measured and self‐reported obesity in US adult women. A Monte Carlo simulation approach was used to model the attributable fraction and preventable number, accounting for uncertainty in the estimates for: 1 strength of the association with obesity, 2 obesity prevalence, and 3 outcome prevalence. Results: Eliminating the impact of prepregnancy obesity would potentially prevent the highest numbers of four outcomes: fetal deaths (6,990; uncertainty interval [UI] 4,110‐10,080), congenital heart defects (2,850; UI 1,035‐5,065), hydrocephalus (490; UI 150‐850), and spina bifida (405; UI 305‐505). If 10% of women with prepregnancy obesity achieved a healthy weight before pregnancy or otherwise mitigated the impact of obesity, nearly 300 congenital heart defects and 700 fetal deaths per year could potentially be prevented. Conclusion: This simulation suggests that effective prevention strategies to reduce prepregnancy obesity or the risk associated with obesity could have a measurable impact on infant health in the US.     

The effect of maternal exposure to endocrine disrupting chemicals on fetal and neonatal development: A review on the major concerns

There is a widespread exposure of general population, including pregnant women and developing fetuses, to the endocrine disrupting chemicals (EDCs). These chemicals have been reported to be present in urine, blood serum, breast milk, and amniotic fluid. Endocrine disruptions induced by environmental toxicants have placed a heavy burden on society, since environmental exposures during critical periods of development can permanently reprogram normal physiological responses, thereby increasing susceptibility to disease later in life—a process known as developmental reprogramming. During development, organogenesis and tissue differentiation occur through a continuous series of tightly‐regulated and precisely‐timed molecular, biochemical, and cellular events. Humans may encounter EDCs daily and during all stages of life, from conception and fetal development through adulthood and senescence. Nevertheless, prenatal and early postnatal windows are the most critical for proper development, due to rapid changes in system growth. Although there are still gaps in our knowledge, currently available data support the urgent need for health and environmental policies aimed at protecting the public and, in particular, the developing fetus and women of reproductive age. Birth Defects Research (Part C) 108:224–242, 2016. © 2016 Wiley Periodicals, Inc.     

Approaches to Refining Estimates of Global Burden and Economics of Dengue

Dengue presents a formidable and growing global economic and disease burden, with around half the world''s population estimated to be at risk of infection. There is wide variation and substantial uncertainty in current estimates of dengue disease burden and, consequently, on economic burden estimates. Dengue disease varies across time, geography and persons affected. Variations in the transmission of four different viruses and interactions among vector density and host''s immune status, age, pre-existing medical conditions, all contribute to the disease''s complexity. This systematic review aims to identify and examine estimates of dengue disease burden and costs, discuss major sources of uncertainty, and suggest next steps to improve estimates. Economic analysis of dengue is mainly concerned with costs of illness, particularly in estimating total episodes of symptomatic dengue. However, national dengue disease reporting systems show a great diversity in design and implementation, hindering accurate global estimates of dengue episodes and country comparisons. A combination of immediate, short-, and long-term strategies could substantially improve estimates of disease and, consequently, of economic burden of dengue. Suggestions for immediate implementation include refining analysis of currently available data to adjust reported episodes and expanding data collection in empirical studies, such as documenting the number of ambulatory visits before and after hospitalization and including breakdowns by age. Short-term recommendations include merging multiple data sources, such as cohort and surveillance data to evaluate the accuracy of reporting rates (by health sector, treatment, severity, etc.), and using covariates to extrapolate dengue incidence to locations with no or limited reporting. Long-term efforts aim at strengthening capacity to document dengue transmission using serological methods to systematically analyze and relate to epidemiologic data. As promising tools for diagnosis, vaccination, vector control, and treatment are being developed, these recommended steps should improve objective, systematic measures of dengue burden to strengthen health policy decisions.     

Deaths and Medical Visits Attributable to Environmental Pollution in the United Arab Emirates

Background

This study estimates the potential health gains achievable in the United Arab Emirates (UAE) with improved controls on environmental pollution. The UAE is an emerging economy in which population health risks have shifted rapidly from infectious diseases to chronic conditions observed in developed nations. The UAE government commissioned this work as part of an environmental health strategic planning project intended to address this shift in the nature of the country’s disease burden.

Methods and Findings

We assessed the burden of disease attributable to six environmental exposure routes outdoor air, indoor air, drinking water, coastal water, occupational environments, and climate change. For every exposure route, we integrated UAE environmental monitoring and public health data in a spatially resolved Monte Carlo simulation model to estimate the annual disease burden attributable to selected pollutants. The assessment included the entire UAE population (4.5 million for the year of analysis). The study found that outdoor air pollution was the leading contributor to mortality, with 651 attributable deaths (95% confidence interval [CI] 143–1,440), or 7.3% of all deaths. Indoor air pollution and occupational exposures were the second and third leading contributors to mortality, with 153 (95% CI 85–216) and 46 attributable deaths (95% CI 26–72), respectively. The leading contributor to health-care facility visits was drinking water pollution, to which 46,600 (95% CI 15,300–61,400) health-care facility visits were attributed (about 15% of the visits for all the diseases considered in this study). Major study limitations included (1) a lack of information needed to translate health-care facility visits to quality-adjusted-life-year estimates and (2) insufficient spatial coverage of environmental data.

Conclusions

Based on international comparisons, the UAE’s environmental disease burden is low for all factors except outdoor air pollution. From a public health perspective, reducing pollutant emissions to outdoor air should be a high priority for the UAE’s environmental agencies.     

High risk maternal factors related to fetal wastage in rural Bangladesh

An analysis of the relationship between fetal mortality (early fetal death and stillbirth), pregnancy order, maternal age, and previous fetal deaths in a rural Bangladesh population characterized by high fertility and mortality and the virtual absence of obstetric and other medical care indicates that early fetal wastage and stillbirth are higher among pregnancy orders 1 and 6, or higher than among orders 2 and 3, with the increased risk particularly apparent among those pregnancies following 2 or more previous fetal deaths. The data consist of the 21,144 pregnancies that occurred to the women in Matlab, Bangladesh, 1966-1969. By a multiple regression technique allowing for pregnancy order and previous fetal deaths, adjustments were made for age of the mother, and after allowances were made for previous fetal deaths, adjustments were made for pregnancy order. Results show the fewest fetal deaths in 2nd and 3rd pregnancies, and most at the highest parities. 10% of all pregnancy terminations 1966-1969 were registered as fetal deaths. Women in the higher pregnancy orders who have not experienced previous fetal deaths or only 1 fetal death have only a slight increase in the risk of fetal death compared to women in pregnancy orders 2 and 3. It is concluded that the virtual absence of medical care facilities is responsible for the large numbers of fetal deaths due to complications of gestation, delivery, and environmental influences. It also results in a higher maternal mortality of women with pregnancy complications related to fetal deaths. This absence of obstetric care and the high maternal mortality in this population may allow only women without reproductive impairments to reach the higher pregnancy orders.     

Reproductive failure in macaques

Reproductive failure among captive and free-ranging macaques is common. Many females experience amenorrhea or anovular cycles. Females who successfully conceive often lose the conceptus before implantation. After implantation, fetuses are aborted because of maternal, paternal, fetal, or placental abnormalities. Death postpartum is likely if infants are premature or if animals are subject to social stress, especially trauma. Based on published reports, reproductive failure among macaques includes an average of 16.3% abortions, 9.9% stillbirths, 21.9% neonatal deaths, and 15.2% infant deaths.     

The Impact of Exposure Misclassification on Associations Between Prepregnancy BMI and Adverse Pregnancy Outcomes

Prepregnancy BMI is a widely used marker of maternal nutritional status that relies on maternal self‐report of prepregnancy weight and height. Pregravid BMI has been associated with adverse health outcomes for the mother and infant, but the impact of BMI misclassification on measures of effect has not been quantified. The authors applied published probabilistic bias analysis methods to quantify the impact of exposure misclassification bias on well‐established associations between self‐reported prepregnancy BMI category and five pregnancy outcomes (small for gestational age (SGA) and large for gestational age (LGA) birth, spontaneous preterm birth (sPTB), gestational diabetes mellitus (GDM), and preeclampsia) derived from a hospital‐based delivery database in Pittsburgh, PA (2003–2005; n = 18,362). The bias analysis method recreates the data that would have been observed had BMI been correctly classified, assuming given classification parameters. The point estimates derived from the bias analysis account for random error as well as systematic error caused by exposure misclassification bias and additional uncertainty contributed by classification errors. In conventional multivariable logistic regression models, underweight women were at increased risk of SGA and sPTB, and reduced risk of LGA, whereas overweight, obese, and severely obese women had elevated risks of LGA, GDM, and preeclampsia compared with normal‐weight women. After applying the probabilistic bias analysis method, adjusted point estimates were attenuated, indicating the conventional estimates were biased away from the null. However, the majority of relations remained readily apparent. This analysis suggests that in this population, associations between self‐reported prepregnancy BMI and pregnancy outcomes are slightly overestimated.     

The global burden of snakebite: a literature analysis and modelling based on regional estimates of envenoming and deaths

Background

Envenoming resulting from snakebites is an important public health problem in many tropical and subtropical countries. Few attempts have been made to quantify the burden, and recent estimates all suffer from the lack of an objective and reproducible methodology. In an attempt to provide an accurate, up-to-date estimate of the scale of the global problem, we developed a new method to estimate the disease burden due to snakebites.

Methods and Findings

The global estimates were based on regional estimates that were, in turn, derived from data available for countries within a defined region. Three main strategies were used to obtain primary data: electronic searching for publications on snakebite, extraction of relevant country-specific mortality data from databases maintained by United Nations organizations, and identification of grey literature by discussion with key informants. Countries were grouped into 21 distinct geographic regions that are as epidemiologically homogenous as possible, in line with the Global Burden of Disease 2005 study (Global Burden Project of the World Bank). Incidence rates for envenoming were extracted from publications and used to estimate the number of envenomings for individual countries; if no data were available for a particular country, the lowest incidence rate within a neighbouring country was used. Where death registration data were reliable, reported deaths from snakebite were used; in other countries, deaths were estimated on the basis of observed mortality rates and the at-risk population. We estimate that, globally, at least 421,000 envenomings and 20,000 deaths occur each year due to snakebite. These figures may be as high as 1,841,000 envenomings and 94,000 deaths. Based on the fact that envenoming occurs in about one in every four snakebites, between 1.2 million and 5.5 million snakebites could occur annually.

Conclusions

Snakebites cause considerable morbidity and mortality worldwide. The highest burden exists in South Asia, Southeast Asia, and sub-Saharan Africa.     

Control of snakebite envenoming: A mathematical modeling study

A mathematical model is designed to assess the impact of some interventional strategies for curtailing the burden of snakebite envenoming in a community. The model is fitted with real data set. Numerical simulations have shown that public health awareness of the susceptible individuals on snakebite preventive measures could reduce the number of envenoming and prevent deaths and disabilities in the population. The simulations further revealed that if at least fifty percent of snakebite envenoming patients receive early treatment with antivenom a substantial number of deaths will be averted. Furthermore, it is shown using optimal control that combining public health awareness and antivenom treatment averts the highest number of snakebite induced deaths and disability adjusted life years in the study area. To choose the best strategy amidst limited resources in the study area, cost effectiveness analysis in terms of incremental cost effectiveness ratio is performed. It has been established that the control efforts of combining public health awareness of the susceptible individuals and antivenom treatment for victims of snakebite envenoming is the most cost effective strategy. Approximately the sum of US$72,548 is needed to avert 117 deaths or 2,739 disability adjusted life years that are recorded within 21 months in the study area. Thus, the combination of these two control strategies is recommended.     

Developmental Origins of Pregnancy Loss in the Adult Female Common Marmoset Monkey (Callithrix jacchus)

Background

The impact of the intrauterine environment on the developmental programming of adult female reproductive success is still poorly understood and potentially underestimated. Litter size variation in a nonhuman primate, the common marmoset monkey (Callithrix jacchus), allows us to model the effects of varying intrauterine environments (e.g. nutrient restriction, exposure to male womb-mates) on the risk of losing fetuses in adulthood. Our previous work has characterized the fetuses of triplet pregnancies as experiencing intrauterine nutritional restriction.

Methodology/Principal Findings

We used over a decade of demographic data from the Southwest National Primate Research Center common marmoset colony. We evaluated differences between twin and triplet females in the number of pregnancies they produce and the proportion of those pregnancies that ended in fetal loss. We found that triplet females produced the same number of total offspring as twin females, but lost offspring during pregnancy at a significantly higher rate than did twins (38% vs. 13%, p = 0.02). Regardless of their own birth weight or the sex ratio of the litter the experienced as fetuses, triplet females lost more fetuses than did twins. Females with a male littermate experienced a significant increase in the proportion of stillbirths.

Conclusions/Significance

These striking findings anchor pregnancy loss in the mother’s own fetal environment and development, underscoring a "Womb to Womb" view of the lifecourse and the intergenerational consequences of development. This has important translational implications for understanding the large proportion of human stillbirths that are unexplained. Our findings provide strong evidence that a full understanding of mammalian life history and reproductive biology requires a developmental foundation.     

Nominations sought for Mindel C. Sheps Award

Abstract

The relationship between early fetal wastage or stillbirth and pregnancy spacing was examined in a population characterized by prolonged lactation, minimal nutrition, and high fertility and mortality. The highest risk of early fetal death was found among those pregnancies conceived less than twelve months after the birth of a surviving breast‐fed infant. Lactation as a possible causal factor is discussed. A significant inverse relationship was apparent for second trimester fetal deaths and pregnancy intervals, but not for third trimester deaths. This finding is surprising when one considers that fetal weight gain, and presumably nutrient demand, increases most rapidly during the third trimester.     

Reproductive compensation in human populations

Reproductive compensation was studied in Russian (family planning) and Middle-Asian (with natural reproduction) urban and rural populations. Questionnaires were used describing postreproductive-age women having at least one pregnancy. The presence of reproductive compensation in a population was identified by comparison of two groups: "loaded" and "unloaded" by values of total and effective fertility. Families with excessive (compared with the mean population value) pregnancy outcome failure (spontaneous abortions, stillbirths, preproductive-age deaths of children) were ascribed to the loaded group. Reproductive compensation was discovered in all populations studied, which indicates that this phenomenon is wide-spread in human populations.     

Estimating Influenza Deaths in Canada, 1992–2009

Background

Poisson regression modelling has been widely used to estimate the disease burden attributable to influenza, though not without concerns that some of the excess burden could be due to other causes. This study aims to provide annual estimates of the mortality and hospitalization burden attributable to both seasonal influenza and the 2009 A/H1N1 pandemic influenza for Canada, and to discuss issues related to the reliability of these estimates.

Methods

Weekly time-series for all-cause mortality and regression models were used to estimate the number of deaths in Canada attributable to influenza from September 1992 to December 2009. To assess their robustness, the annual estimates derived from different parameterizations of the regression model for all-cause mortality were compared. In addition, the association between the annual estimates for mortality and hospitalization by age group, underlying cause of death or primary reason for admission and discharge status is discussed.

Results

The crude influenza-attributed mortality rate based on all-cause mortality and averaged over 17 influenza seasons prior to the 2009 A/H1N1 pandemic was 11.3 (95%CI, 10.5 - 12.1) deaths per 100 000 population per year, or an average of 3,500 (95%CI, 3,200 - 3,700) deaths per year attributable to seasonal influenza. The estimated annual rates ranged from undetectable at the ecological level to more than 6000 deaths per year over the three A/Sydney seasons. In comparison, we attributed an estimated 740 deaths (95%CI, 350–1500) to A(H1N1)pdm09. Annual estimates from different model parameterizations were strongly correlated, as were estimates for mortality and morbidity; the higher A(H1N1)pdm09 burden in younger age groups was the most notable exception.

Interpretation

With the exception of some of the Serfling models, differences in the ecological estimates of the disease burden attributable to influenza were small in comparison to the variation in disease burden from one season to another.     

Evaluation of 100 autopsies performed in the maternity service of the H?tel-Dieu in Lyon during an 18 month period

100 Necropsies have been performed from January 1983 to June 1984, on 53 abortus and stillborn and 47 therapeutic terminations of pregnancy. All fetuses came from the same obstetric unit. Half spontaneous fetal deaths remained of unknown aetiology; in 18 cases (34%) placental, maternal or pregnancy pathology existed; fetal abnormalities were discovered in 10 (18%). As for therapeutic interruptions of pregnancy (the indications of which are detailed) the importance of ultrasonography emphasized since this technique allowed 25 of the 47 prenatal diagnosis. The importance of necropsy to help precise diagnosis and subsequent counselling is also recalled.     

Fetal and maternal factors associated with infant mortality in vervet monkeys

Background Causes of infant death remain unknown in significant proportions of human and non‐human primate pregnancies. Methods A closed breeding colony with high rates of infant mortality had pregnancies assessed (n = 153) by fetal measurements and maternal characteristics. Infant outcome was classified as neonatal death (stillborn or died <48 hours from birth), postnatal death (died 2–30 days) or surviving (alive after 30 days). Results Fetal size did not predict outcome. Poor maternal glycemic control and low social ranking increased odds for adverse outcome (OR = 3.72, P = 0.01 and 2.27, P = 0.04, respectively). Male sex was over‐represented in stillbirths (P = 0.04), and many were macrosomic, but size did not associate with maternal glycemic control measured as glycated hemoglobin A1c. Postnatally dead infants were smaller (P < 0.01), which associated with behavioral factors and glycemic control. Conclusions Fetal growth estimates predicted gestational age but not fetal outcome. Maternal social status and metabolic health, particularly glycemic control, increased risks of adverse pregnancy outcome.