Estimates of the global, regional, and national morbidity, mortality, and aetiologies of diarrhoea in 195 countries: a systematic analysis for the Global Burden of Disease Study 2016.

BACKGROUND: The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016 provides an up-to-date analysis of the burden of diarrhoea in 195 countries. This study assesses cases, deaths, and aetiologies in 1990-2016 and assesses how the burden of diarrhoea has changed in people of all ages. METHODS: We modelled diarrhoea mortality with a Bayesian hierarchical modelling platform that evaluates a wide range of covariates and model types on the basis of vital registration and verbal autopsy data. We modelled diarrhoea incidence with a compartmental meta-regression tool that enforces an association between incidence and prevalence, and relies on scientific literature, population representative surveys, and health-care data. Diarrhoea deaths and episodes were attributed to 13 pathogens by use of a counterfactual population attributable fraction approach. Diarrhoea risk factors are also based on counterfactual estimates of risk exposure and the association between the risk and diarrhoea. Each modelled estimate accounted for uncertainty. FINDINGS: In 2016, diarrhoea was the eighth leading cause of death among all ages (1 655 944 deaths, 95% uncertainty interval [UI] 1 244 073-2 366 552) and the fifth leading cause of death among children younger than 5 years (446 000 deaths, 390 894-504 613). Rotavirus was the leading aetiology for diarrhoea mortality among children younger than 5 years (128 515 deaths, 105 138-155 133) and among all ages (228 047 deaths, 183 526-292 737). Childhood wasting (low weight-for-height score), unsafe water, and unsafe sanitation were the leading risk factors for diarrhoea, responsible for 80·4% (95% UI 68·2-85·0), 72·1% (34·0-91·4), and 56·4% (49·3-62·7) of diarrhoea deaths in children younger than 5 years, respectively. Prevention of wasting in 1762 children (95% UI 1521-2170) could avert one death from diarrhoea. INTERPRETATION: Substantial progress has been made globally in reducing the burden of diarrhoeal diseases, driven by decreases in several primary risk factors. However, this reduction has not been equal across locations, and burden among adults older than 70 years requires attention. FUNDING: Bill & Melinda Gates Foundation.

Estimates of the global, regional, and national morbidity, mortality, and aetiologies of lower respiratory infections in 195 countries, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016.

BACKGROUND: Lower respiratory infections are a leading cause of morbidity and mortality around the world. The Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study 2016, provides an up-to-date analysis of the burden of lower respiratory infections in 195 countries. This study assesses cases, deaths, and aetiologies spanning the past 26 years and shows how the burden of lower respiratory infection has changed in people of all ages. METHODS: We used three separate modelling strategies for lower respiratory infections in GBD 2016: a Bayesian hierarchical ensemble modelling platform (Cause of Death Ensemble model), which uses vital registration, verbal autopsy data, and surveillance system data to predict mortality due to lower respiratory infections; a compartmental meta-regression tool (DisMod-MR), which uses scientific literature, population representative surveys, and health-care data to predict incidence, prevalence, and mortality; and modelling of counterfactual estimates of the population attributable fraction of lower respiratory infection episodes due to Streptococcus pneumoniae, Haemophilus influenzae type b, influenza, and respiratory syncytial virus. We calculated each modelled estimate for each age, sex, year, and location. We modelled the exposure level in a population for a given risk factor using DisMod-MR and a spatio-temporal Gaussian process regression, and assessed the effectiveness of targeted interventions for each risk factor in children younger than 5 years. We also did a decomposition analysis of the change in LRI deaths from 2000-16 using the risk factors associated with LRI in GBD 2016. FINDINGS: In 2016, lower respiratory infections caused 652 572 deaths (95% uncertainty interval [UI] 586 475-720 612) in children younger than 5 years (under-5s), 1 080 958 deaths (943 749-1 170 638) in adults older than 70 years, and 2 377 697 deaths (2 145 584-2 512 809) in people of all ages, worldwide. Streptococcus pneumoniae was the leading cause of lower respiratory infection morbidity and mortality globally, contributing to more deaths than all other aetiologies combined in 2016 (1 189 937 deaths, 95% UI 690 445-1 770 660). Childhood wasting remains the leading risk factor for lower respiratory infection mortality among children younger than 5 years, responsible for 61·4% of lower respiratory infection deaths in 2016 (95% UI 45·7-69·6). Interventions to improve wasting, household air pollution, ambient particulate matter pollution, and expanded antibiotic use could avert one under-5 death due to lower respiratory infection for every 4000 children treated in the countries with the highest lower respiratory infection burden. INTERPRETATION: Our findings show substantial progress in the reduction of lower respiratory infection burden, but this progress has not been equal across locations, has been driven by decreases in several primary risk factors, and might require more effort among elderly adults. By highlighting regions and populations with the highest burden, and the risk factors that could have the greatest effect, funders, policy makers, and programme implementers can more effectively reduce lower respiratory infections among the world's most susceptible populations. FUNDING: Bill & Melinda Gates Foundation.

Estimates of the global, regional, and national morbidity, mortality, and aetiologies of lower respiratory tract infections in 195 countries: a systematic analysis for the Global Burden of Disease Study 2015.

BACKGROUND: The Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study 2015 provides an up-to-date analysis of the burden of lower respiratory tract infections (LRIs) in 195 countries. This study assesses cases, deaths, and aetiologies spanning the past 25 years and shows how the burden of LRI has changed in people of all ages. METHODS: We estimated LRI mortality by age, sex, geography, and year using a modelling platform shared across most causes of death in the GBD 2015 study called the Cause of Death Ensemble model. We modelled LRI morbidity, including incidence and prevalence, using a meta-regression platform called DisMod-MR. We estimated aetiologies for LRI using two different counterfactual approaches, the first for viral pathogens, which incorporates the aetiology-specific risk of LRI and the prevalence of the aetiology in LRI episodes, and the second for bacterial pathogens, which uses a vaccine-probe approach. We used the Socio-demographic Index, which is a summary indicator derived from measures of income per capita, educational attainment, and fertility, to assess trends in LRI-related mortality. The two leading risk factors for LRI disability-adjusted life-years (DALYs), childhood undernutrition and air pollution, were used in a decomposition analysis to establish the relative contribution of changes in LRI DALYs. FINDINGS: In 2015, we estimated that LRIs caused 2·74 million deaths (95% uncertainty interval [UI] 2·50 million to 2·86 million) and 103·0 million DALYs (95% UI 96·1 million to 109·1 million). LRIs have a disproportionate effect on children younger than 5 years, responsible for 704 000 deaths (95% UI 651 000-763 000) and 60.6 million DALYs (95ÙI 56·0-65·6). Between 2005 and 2015, the number of deaths due to LRI decreased by 36·9% (95% UI 31·6 to 42·0) in children younger than 5 years, and by 3·2% (95% UI -0·4 to 6·9) in all ages. Pneumococcal pneumonia caused 55·4% of LRI deaths in all ages, totalling 1 517 388 deaths (95% UI 857 940-2 183 791). Between 2005 and 2015, improvements in air pollution exposure were responsible for a 4·3% reduction in LRI DALYs and improvements in childhood undernutrition were responsible for an 8·9% reduction. INTERPRETATION: LRIs are the leading infectious cause of death and the fifth-leading cause of death overall; they are the second-leading cause of DALYs. At the global level, the burden of LRIs has decreased dramatically in the last 10 years in children younger than 5 years, although the burden in people older than 70 years has increased in many regions. LRI remains a largely preventable disease and cause of death, and continued efforts to decrease indoor and ambient air pollution, improve childhood nutrition, and scale up the use of the pneumococcal conjugate vaccine in children and adults will be essential in reducing the global burden of LRI. FUNDING: Bill & Melinda Gates Foundation.

[Does the hospital cost of care differ for inflammatory bowel disease patients with or without gastrointestinal infections? A case-control study]. / Unterscheiden sich die Behandlungskosten bei stationär betreuten Patienten mit einer chronisch-entzündlichen Darmerkrankung mit und ohne gastrointestinale Infektionen? Eine Fallkontrollstudie.

OBJECTIVE: Gastrointestinal Infections have been implicated as possible causes of exacerbation of inflammatory bowel disease (IBD) or risk factors for severe flares in general. The introduction of the G-DRG reimbursement system has greatly increased the pressure to provide cost effective treatment in German hospitals. Few studies have compared the costs of treating IBD patients with or without gastrointestinal infections and none of them have specifically considered the German reimbursement situation. METHODS: We performed a single center case-control retrospective chart review from 2002 to 2011 of inpatients with IBD (Department of Internal Medicine IV, University Hospital Jena) with an exacerbation of their disease. The presence of gastrointestinal infections (Salmonella, Shigella, Campylobacter, Yersinia, adeno-, rota-, norovirus and Clostridium difficile) was assessed in all inpatients with Cohn's disease (CD) and ulcerative colitis (UC). IBD patients with gastrointestinal infections (n = 79) were matched for age to IBD patients who were negative for gastrointestinal pathogens (n = 158). Patient level costing (PLC) was used to express the total cost of hospital care for each patient; PLC comprised a weighted daily bed cost plus cost of all medical services provided (e. g., endoscopy, microbiology, pathology) calculated according to an activity-based costing approach. All costs were discounted to 2012 values. RESULTS: Gastrointestinal infections in IBD patients were not associated with an increase in mortality (0%); however, they were associated with 2.3-fold higher total hospital charges (6499.10 € vs. 2817.00 €; p = 0.001) and increased length of stay in hospital (14.5 vs. 9.4 days; p <  0.0001). Despite increased reimbursement by DRG for IBD patients with gastrointestinal infections compared to patients without infections (3833.90 € vs. 2553.50 €; p = 0.005), hospital care in these patients was substantially underfunded (deficit -2496.80 € vs. -433.10 €) because of increased length of stay with personnel costs, especially in UC. CONCLUSION: Inpatient hospital costs differ significantly for IBD patients with and without gastrointestinal infections, especially in ulcerative colitis, when care was provided in a single university hospital.

The impact of infection on population health: results of the Ontario burden of infectious diseases study.

BACKGROUND: Evidence-based priority setting is increasingly important for rationally distributing scarce health resources and for guiding future health research. We sought to quantify the contribution of a wide range of infectious diseases to the overall infectious disease burden in a high-income setting. METHODOLOGY/PRINCIPAL FINDINGS: We used health-adjusted life years (HALYs), a composite measure comprising premature mortality and reduced functioning due to disease, to estimate the burden of 51 infectious diseases and associated syndromes in Ontario using 2005-2007 data. Deaths were estimated from vital statistics data and disease incidence was estimated from reportable disease, healthcare utilization, and cancer registry data, supplemented by local modeling studies and national and international epidemiologic studies. The 51 infectious agents and associated syndromes accounted for 729 lost HALYs, 44.2 deaths, and 58,987 incident cases per 100,000 population annually. The most burdensome infectious agents were: hepatitis C virus, Streptococcus pneumoniae, Escherichia coli, human papillomavirus, hepatitis B virus, human immunodeficiency virus, Staphylococcus aureus, influenza virus, Clostridium difficile, and rhinovirus. The top five, ten, and 20 pathogens accounted for 46%, 67%, and 75% of the total infectious disease burden, respectively. Marked sex-specific differences in disease burden were observed for some pathogens. The main limitations of this study were the exclusion of certain infectious diseases due to data availability issues, not considering the impact of co-infections and co-morbidity, and the inability to assess the burden of milder infections that do not result in healthcare utilization. CONCLUSIONS/SIGNIFICANCE: Infectious diseases continue to cause a substantial health burden in high-income settings such as Ontario. Most of this burden is attributable to a relatively small number of infectious agents, for which many effective interventions have been previously identified. Therefore, these findings should be used to guide public health policy, planning, and research.

Immunohistochemical assessment of respiratory viruses in necropsy samples from lethal non-pandemic seasonal respiratory infections.

BACKGROUND/AIM: Acute respiratory infections are an important cause of childhood morbidity and mortality throughout the world, and viruses have often been reported to be an aetiological agent. This study aimed to identify respiratory viruses in paraffin-embedded samples of paediatric lung necropsy specimens, using immunohistochemistry on tissue microarray slides. METHODS: Retrospective study in 200 lung tissue samples from children who had died from severe respiratory infections during 1985-2005. Immunoperoxidase assay was performed to detect the viruses that were most commonly associated with respiratory tract infections: influenza virus A (FLU A), influenza virus B (FLU B), respiratory syncytial virus (RSV), adenovirus (AdV) and parainfluenza virus (PIV) types 1, 2 and 3. RESULTS: Viruses were detected in 71 (35.5%) cases. Most positive cases were observed in children younger than 6 months. In 42.3% of cases, only one virus was detected: 11 (36.7%) RSV; 7 (23.3%) AdV; 4 (13.3%) PIV2; 3 (10%) FLU A; 2 (6.7%) FLU B; 2 (6.7%) PIV3; and 1 (3.3%) PIV1. Co-infection with more than one virus was observed in 41 (57.7%) cases. No positive correlations were observed between the presence of viral antigens and seasonality of the infection, sex, age or histopathological findings. CONCLUSIONS: Non-pandemic seasonal respiratory viruses are involved in a significant number of deaths in paediatric patients; these findings highlight the importance of laboratory investigation of these agents in patients hospitalised with severe acute respiratory infections.

Estimating the costs of achieving the WHO-UNICEF Global Immunization Vision and Strategy, 2006-2015.

OBJECTIVE: To estimate the cost of scaling up childhood immunization services required to reach the WHO-UNICEF Global Immunization Vision and Strategy (GIVS) goal of reducing mortality due to vaccine-preventable diseases by two-thirds by 2015. METHODS: A model was developed to estimate the total cost of reaching GIVS goals by 2015 in 117 low- and lower-middle- income countries. Current spending was estimated by analysing data from country planning documents, and scale-up costs were estimated using a bottom-up, ingredients-based approach. Financial costs were estimated by country and year for reaching 90% coverage with all existing vaccines; introducing a discrete set of new vaccines (rotavirus, conjugate pneumococcal, conjugate meningococcal A and Japanese encephalitis); and conducting immunization campaigns to protect at-risk populations against polio, tetanus, measles, yellow fever and meningococcal meningitis. FINDINGS: The 72 poorest countries of the world spent US$ 2.5 (range: US$ 1.8-4.2) billion on immunization in 2005, an increase from US$ 1.1 (range: US$ 0.9-1.6) billion in 2000. By 2015 annual immunization costs will on average increase to about US$ 4.0 (range US$ 2.9-6.7) billion. Total immunization costs for 2006-2015 are estimated at US$ 35 (range US$ 13-40) billion; of this, US$ 16.2 billion are incremental costs, comprised of US$ 5.6 billion for system scale-up and US$ 8.7 billion for vaccines; US$ 19.3 billion is required to maintain immunization programmes at 2005 levels. In all 117 low- and lower-middle-income countries, total costs for 2006-2015 are estimated at US$ 76 (range: US$ 23-110) billion, with US$ 49 billion for maintaining current systems and $27 billion for scaling-up. CONCLUSION: In the 72 poorest countries, US$ 11-15 billion (30%-40%) of the overall resource needs are unmet if the GIVS goals are to be reached. The methods developed in this paper are approximate estimates with limitations, but provide a roadmap of financing gaps that need to be filled to scale up immunization by 2015.

The global value of vaccination.

While most agree that vaccination is one of the most important public health practices, vaccines continue to be underused and undervalued, and vaccine-preventable diseases remain a threat to world health. Perhaps one reason this gap remains is that decision-making generally is made on a vaccine-by-vaccine basis. There has been less attention to the value of vaccination in general. To more clearly identify this value, this paper reviews the cost-effectiveness literature and calculates the annual benefits of vaccination on a global scale.

Clinical and financial benefits of rapid detection of respiratory viruses: an outcomes study.

To assess the expected benefits of rapid reporting of respiratory viruses, we compared patients whose samples were processed using standard techniques such as enzyme immunoassays, shell vial assays, and culture tube assays (year 1) to patients whose samples were processed with the same standard techniques in addition to immunofluorescent testing (FA) directly on cytocentrifuged samples (year 2). The cytospin FA screened for influenza A and B viruses, respiratory syncytial virus (RSV), parainfluenza viruses 1 to 3, and adenovirus (DAKO Diagnostics Ltd.). The specificity of the cytospin FA for all viruses was 100%. The sensitivities for influenza A virus and RSV were 90 and 98%, respectively, but the sensitivities for influenza B virus and adenovirus were unacceptable (14.3 and 0%, respectively). However, since the former viruses account for >85% of our isolates from clinical specimens, the cytospin FA is an excellent screening test since the positive result was available within hours. The mean turnaround time for all positive viruses was 4.5 days in year 1 and 0.9 day in year 2 (P = 0.001). This rapid reporting resulted in physicians having access to information sooner, enabling more appropriate treatment. The mean length of stay in the hospital for inpatients with respiratory viral isolates was 10.6 days for year 1 versus 5.3 days for year 2. Mean variable costs for these patients was $7,893 in year 1 and $2,177 in year 2. After subtracting reagent costs and technological time, the savings in variable costs was $144,332/year. Summarizing, the cytospin FA markedly decreased turnaround time and was associated with decreased mortality, length of stay, and costs and with better antibiotic stewardship.

The cost-effectiveness of reducing donor exposures with single-donor versus pooled random-donor platelets.

BACKGROUND: Single-donor platelets (SDPs) are frequently preferred over pooled random-donor platelets (RDPs) to reduce donor exposures and the risk for virus transmission or HLA alloimmunization. Transfusion-associated virus-transmission risks have significantly decreased, which suggests that white cell reduction by filtration eliminates any difference in the risk of alloimmunization in transfused leukemic patients. Health care reform pressures of make it appropriate to examine the cost-effectiveness of SDPs versus RDPs in reducing donor exposures. STUDY DESIGN AND METHODS: A decision analysis model was developed and sensitivity analyses were used to assess the incremental cost (dollars/quality-adjusted life-year) associated with the use of SDPs versus RDPs for adult patients undergoing hematopoietic progenitor cell transplantation or primary coronary artery bypass grafting (CABG). RESULTS: Among transplant patients, the incremental cost of choosing SDPs as opposed to RDPs ranged from $168,700 to $519,822 per quality-adjusted life-year. For patients undergoing primary CABG, the incremental cost was $192,415 (females) and $216,280 (males). Variations in the cost differential between SDPs and RDPs, the number of random-donor platelets in the RDP, and the risk of bacterial sepsis markedly influenced cost-effectiveness. The model was minimally affected by variations in the risks of transmission of HIV and hepatitis B and C, and human T-lymphotropic viruses. CONCLUSION: In comparison with other accepted medical interventions, the use of SDPs as opposed to RDPs may not be a cost-effective method of reducing donor exposures in the adult patient populations studied. SDPs were more cost-effective in patients undergoing primary CABG than in leukemia patients undergoing hematopoietic progenitor cell transplantation. Regardless of diagnosis, decreasing the acquisition cost differential would have the greatest impact on improving the cost-effectiveness of SDPs, as opposed to RDPs, to decrease donor exposures.

Risk assessment of virus in drinking water.

The reevaluation of drinking water treatment practices in a desire to minimize the formation of disinfection byproducts while assuring minimum levels of public health protection against infectious organisms has caused it to become necessary to consider the problem of estimation of risks posed from exposure to low levels of microorganisms, such as virus or protozoans, found in treated drinking water. This paper outlines a methodology based on risk assessment principles to approach the problem. The methodology is validated by comparison with results obtained in a prospective epidemiological study. It is feasible to produce both point and interval estimates of infection, illness and perhaps mortality by this methodology. Areas of uncertainty which require future data are indicated.

Economic impact of an epizootic of bovine vesicular stomatitis in California.

A recent outbreak of vesicular stomatitis in California's San Joaquin Valley caused economic loss at 2 dairies of $225,000 during a 2-month period. These losses amounted to $202/cow for dairy 1 and $97/cow for dairy 2. The most notable economic losses were associated with high cull rates. The rapid spread of the disease (attack rates were 72% in 66 days for dairy 1 and 38% in 41 days for dairy 2) suggests that high-density herds particularly may be vulnerable to the disease. Factors that may have accounted for this rapid spread included common water troughs, open corrals, and inability of the dairy operator to isolate cows due to lack of space.

Economic impact of rotavirus and other neonatal disease agents of animals.

Methods for estimating the economic impact of disease agents were developed and utilized to assess the relative economic importance of rotavirus and other disease agents in calves. Based on incidence data from 2 sources, Escherichia coli was responsible for the most devastating economic losses (50.9% and 74.6%). Coronaviral (17.5% and 29.7% loss) and rotaviral (3.2% and 9.1% loss) infections ranked 2nd and 3rd, respectively. In one study, cryptosporidial infections (6.5% loss) were estimated to be similar in economic impact to rotaviral infection. Salmonellosis, mycotic gastroenteritis, infectious bovine rhinotracheitis, and bovine viral diarrhea infections accounted for minor losses. The estimated average annual loss of calves for the 7-year period, 1970 through 1976, was $95,500,000/year. Based on data from 2 studies, the estimated average annual loss from E coli was $48.6 and 71.2 million; from coronaviral infection, $16.7 and 28.4 million; from rotaviral infection, $3.1 and $8.7 million; and from cryptosporidial infection, from 1 study, $6.2 million. Estimates of economic impact of disease agents on calves, and likely in other species, indicate that rotaviral infections have a relatively minor role with respect to E coli and coronaviral infections.