Global and Regional Estimates for Subtype-Specific Therapeutic and Prophylactic HIV-1 Vaccines: A Modeling Study.
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ABSTRACT:
SUBMITTER: Elangovan R
PROVIDER: S-EPMC8320730 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Immunoglobulin E-mediated allergies affect more than 25% of the population. Allergen exposure induces a variety of symptoms in allergic patients, which include rhinitis, conjunctivitis, asthma, dermatitis, food allergy and life-threatening systemic anaphylaxis. At present, allergen-specific immunotherapy (SIT), which is based on the administration of the disease-causing allergens, is the only disease-modifying treatment for allergy. Current therapeutic allergy vaccines are still prepared from relatively poorly defined allergen extracts. However, with the availability of the structures of the most common allergen molecules, it has become possible to produce well-defined recombinant and synthetic allergy vaccines that allow specific targeting of the mechanisms of allergic disease. Here we provide a summary of the development and mechanisms of SIT, and then review new forms of therapeutic vaccines that are based on recombinant and synthetic molecules. Finally, we discuss possible allergen-specific strategies for prevention of allergic disease.
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Project description:IntroductionFemale sex workers (FSWs) are at high risk of HIV infection. Our objective was to determine the proportion of HIV prevalence in the general female adult population that is attributable to the occupational exposure of female sex work, due to unprotected sexual intercourse.MethodsPopulation attributable fractions of HIV prevalence due to female sex work were estimated for 2011. A systematic search was conducted to retrieve required input data from available sources. Data gaps of HIV prevalence in FSWs for 2011 were filled using multilevel modeling and multivariate linear regression. The fraction of HIV attributable to female sex work was estimated as the excess HIV burden in FSWs deducting the HIV burden in FSWs due to injecting drug use.ResultsAn estimated fifteen percent of HIV in the general female adult population is attributable to (unsafe) female sex work. The region with the highest attributable fraction is Sub Saharan Africa, but the burden is also substantial for the Caribbean, Latin America and South and Southeast Asia. We estimate 106,000 deaths from HIV are a result of female sex work globally, 98,000 of which occur in Sub-Saharan Africa. If HIV prevalence in other population groups originating from sexual contact with FSWs had been considered, the overall attributable burden would probably be much larger.DiscussionFemale sex work is an important contributor to HIV transmission and the global HIV burden. Effective HIV prevention measures exist and have been successfully targeted at key populations in many settings. These must be scaled up.ConclusionFSWs suffer from high HIV burden and are a crucial core population for HIV transmission. Surveillance, prevention and treatment of HIV in FSWs should benefit both this often neglected vulnerable group and the general population.
| S-EPMC3662690 | biostudies-literature
Project description:The focus of most current HIV-1 vaccine development is on antibody-based approaches. This is because certain antibody responses correlated with protection from HIV-1 acquisition in the RV144 phase III trial, and because a series of potent and broad spectrum neutralizing antibodies have been isolated from infected individuals. Taken together, these two findings suggest ways forward to develop a neutralizing antibody-based vaccine. However, understanding of the correlates of protection from disease in HIV-1 and other infections strongly suggests that we should not ignore CTL-based research. Here we review recent progress in the field and highlight the challenges implicit in HIV-1 vaccine design and some potential solutions.
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Project description:Insufficient quantities and inadequate quality of complementary foods, together with poor feeding practices, pose a threat to children's health and nutrition. Interventions to improve complementary feeding are critical to reduce all forms of malnutrition, and access to data to ascertain the status of complementary feeding practices is essential for efforts to improve feeding behaviours. However, sufficient data to generate estimates for the core indicators covering the complementary feeding period only became available recently. The current situation of complementary feeding at the global and regional level is reported here using data contained within the UNICEF global database. Global rates of continued breastfeeding drop from 74.0% at 1 year of age to 46.3% at 2 years of age. Nearly a third of infants 4-5 months old are already fed solid foods, whereas nearly 20% of 10-11 months old had not consumed solid foods during the day prior to their survey. Of particular concern is the low rate (28.2%) of children 6-23 months receiving at least a minimally diverse diet. Although rates for all indicators vary by background characteristics, feeding behaviours are suboptimal even in richest households, suggesting that cultural factors and poor knowledge regarding an adequate diet for young children are important to address. In summary, far too few children are benefitting from minimum complementary feeding practices. Efforts are needed not only to improve children's diets for their survival, growth, and development but also for governments to report on progress against global infant and young child feeding indicators on a regular basis.
| S-EPMC6865887 | biostudies-literature
Project description:BackgroundTimely assessment of the burden of HIV/AIDS is essential for policy setting and programme evaluation. In this report from the Global Burden of Disease Study 2015 (GBD 2015), we provide national estimates of levels and trends of HIV/AIDS incidence, prevalence, coverage of antiretroviral therapy (ART), and mortality for 195 countries and territories from 1980 to 2015.MethodsFor countries without high-quality vital registration data, we estimated prevalence and incidence with data from antenatal care clinics and population-based seroprevalence surveys, and with assumptions by age and sex on initial CD4 distribution at infection, CD4 progression rates (probability of progression from higher to lower CD4 cell-count category), on and off antiretroviral therapy (ART) mortality, and mortality from all other causes. Our estimation strategy links the GBD 2015 assessment of all-cause mortality and estimation of incidence and prevalence so that for each draw from the uncertainty distribution all assumptions used in each step are internally consistent. We estimated incidence, prevalence, and death with GBD versions of the Estimation and Projection Package (EPP) and Spectrum software originally developed by the Joint United Nations Programme on HIV/AIDS (UNAIDS). We used an open-source version of EPP and recoded Spectrum for speed, and used updated assumptions from systematic reviews of the literature and GBD demographic data. For countries with high-quality vital registration data, we developed the cohort incidence bias adjustment model to estimate HIV incidence and prevalence largely from the number of deaths caused by HIV recorded in cause-of-death statistics. We corrected these statistics for garbage coding and HIV misclassification.FindingsGlobal HIV incidence reached its peak in 1997, at 3·3 million new infections (95% uncertainty interval [UI] 3·1-3·4 million). Annual incidence has stayed relatively constant at about 2·6 million per year (range 2·5-2·8 million) since 2005, after a period of fast decline between 1997 and 2005. The number of people living with HIV/AIDS has been steadily increasing and reached 38·8 million (95% UI 37·6-40·4 million) in 2015. At the same time, HIV/AIDS mortality has been declining at a steady pace, from a peak of 1·8 million deaths (95% UI 1·7-1·9 million) in 2005, to 1·2 million deaths (1·1-1·3 million) in 2015. We recorded substantial heterogeneity in the levels and trends of HIV/AIDS across countries. Although many countries have experienced decreases in HIV/AIDS mortality and in annual new infections, other countries have had slowdowns or increases in rates of change in annual new infections.InterpretationScale-up of ART and prevention of mother-to-child transmission has been one of the great successes of global health in the past two decades. However, in the past decade, progress in reducing new infections has been slow, development assistance for health devoted to HIV has stagnated, and resources for health in low-income countries have grown slowly. Achievement of the new ambitious goals for HIV enshrined in Sustainable Development Goal 3 and the 90-90-90 UNAIDS targets will be challenging, and will need continued efforts from governments and international agencies in the next 15 years to end AIDS by 2030.FundingBill & Melinda Gates Foundation, and National Institute of Mental Health and National Institute on Aging, National Institutes of Health.
| S-EPMC5056319 | biostudies-literature
Project description:The incidence of fatal overdoses has increased worldwide due to the widespread access to illicit fentanyl and its potent analogues. Vaccines offer a promising strategy to reduce the prevalence of opioid use disorders (OUDs) and to prevent toxicity from accidental and deliberate exposure to fentanyl and its derivatives. This study describes the development and characterization of vaccine formulations consisting of novel fentanyl-based haptens conjugated to carrier proteins. Vaccine efficacy was tested against opioid-induced behavior and toxicity in mice and rats challenged with fentanyl and its analogues. Prophylactic vaccination reduced fentanyl- and sufentanil-induced antinociception, respiratory depression, and bradycardia in mice and rats. Therapeutic vaccination also reduced fentanyl intravenous self-administration in rats. Because of their selectivity, vaccines did not interfere with the pharmacological effects of commonly used anesthetics nor with methadone, naloxone, oxycodone, or heroin. These preclinical data support the translation of vaccines as a viable strategy to counteract fentanyl use disorders and toxicity.
| S-EPMC8193686 | biostudies-literature
Project description:BackgroundThe development of cognitive and socioemotional skills early in life influences later health and well-being. Existing estimates of unmet developmental potential in low- and middle-income countries (LMICs) are based on either measures of physical growth or proxy measures such as poverty. In this paper we aim to directly estimate the number of children in LMICs who would be reported by their caregivers to show low cognitive and/or socioemotional development.Methods and findingsThe present paper uses Early Childhood Development Index (ECDI) data collected between 2005 and 2015 from 99,222 3- and 4-y-old children living in 35 LMICs as part of the Multiple Indicator Cluster Survey (MICS) and Demographic and Health Surveys (DHS) programs. First, we estimate the prevalence of low cognitive and/or socioemotional ECDI scores within our MICS/DHS sample. Next, we test a series of ordinary least squares regression models predicting low ECDI scores across our MICS/DHS sample countries based on country-level data from the Human Development Index (HDI) and the Nutrition Impact Model Study. We use cross-validation to select the model with the best predictive validity. We then apply this model to all LMICs to generate country-level estimates of the prevalence of low ECDI scores globally, as well as confidence intervals around these estimates. In the pooled MICS and DHS sample, 14.6% of children had low ECDI scores in the cognitive domain, 26.2% had low socioemotional scores, and 36.8% performed poorly in either or both domains. Country-level prevalence of low cognitive and/or socioemotional scores on the ECDI was best represented by a model using the HDI as a predictor. Applying this model to all LMICs, we estimate that 80.8 million children ages 3 and 4 y (95% CI 48.1 million, 113.6 million) in LMICs experienced low cognitive and/or socioemotional development in 2010, with the largest number of affected children in sub-Saharan Africa (29.4.1 million; 43.8% of children ages 3 and 4 y), followed by South Asia (27.7 million; 37.7%) and the East Asia and Pacific region (15.1 million; 25.9%). Positive associations were found between low development scores and stunting, poverty, male sex, rural residence, and lack of cognitive stimulation. Additional research using more detailed developmental assessments across a larger number of LMICs is needed to address the limitations of the present study.ConclusionsThe number of children globally failing to reach their developmental potential remains large. Additional research is needed to identify the specific causes of poor developmental outcomes in diverse settings, as well as potential context-specific interventions that might promote children's early cognitive and socioemotional well-being.
| S-EPMC4896459 | biostudies-literature
Project description:BackgroundA growing literature has documented the high global morbidity, mortality and mental health burden associated with the current Covid-19 pandemic. In this paper, we aimed to quantify the total utility and quality of life loss resulting from Covid-19-related government restrictions imposed at the national, regional and global levels.MethodsWe conducted quality of life online surveys in France, India, Italy, UK and the United States of America between June 21st and September 13th 2021, and used regression models to estimate the average quality of life loss due to light and severe restrictions in these countries. We then combined estimated disutility weights from the pooled sample with the latest data on Covid-19 restrictions exposure in each country to estimate the total disutility generated by restrictions at the national, regional and global level. We also embedded a discrete choice experiment (DCE) into the online survey to estimate average willingness to pay to avoid specific restrictions.FindingsA total of 947 surveys were completed. Thirty-five percent of respondents were female, and 69.5% were between 18 and 39 years old. The weighted average utility weight was 0.71 (95% CIs 0.69-0.74) for light restrictions, and 0.65 (0.63-0.68) for severe restrictions. At the global scale, this implies a total loss of 3259 million QALYs (95% 3021, 3496) as of September 6th, 2021, with the highest burden in lower and upper middle-income countries. Utility losses appear to be particularly large for closures of schools and daycares as well as restaurants and bars, and seem relatively small for wearing masks and travel restrictions.InterpretationThe results presented here suggest that the QALY losses due to restrictions are substantial. Future mitigation strategies should try to balance potential reductions in disease transmission achievable through specific measures against their respective impact on quality of life. Additional research is needed to determine differences in restriction-specific disutilities across countries, and to determine optimal policy responses to similar future disease threats.FundingNo funding was received for this project.
| S-EPMC8856030 | biostudies-literature
Project description:Diarrhoeal diseases are major contributors to the global burden of disease, particularly in children. However, comprehensive estimates of the incidence and mortality due to specific aetiologies of diarrhoeal diseases are not available. The objective of this study is to provide estimates of the global and regional incidence and mortality of diarrhoeal diseases caused by nine pathogens that are commonly transmitted through foods.We abstracted data from systematic reviews and, depending on the overall mortality rates of the country, applied either a national incidence estimate approach or a modified Child Health Epidemiology Reference Group (CHERG) approach to estimate the aetiology-specific incidence and mortality of diarrhoeal diseases, by age and region. The nine diarrhoeal diseases assessed caused an estimated 1.8 billion (95% uncertainty interval [UI] 1.1-3.3 billion) cases and 599,000 (95% UI 472,000-802,000) deaths worldwide in 2010. The largest number of cases were caused by norovirus (677 million; 95% UI 468-1,153 million), enterotoxigenic Escherichia coli (ETEC) (233 million; 95% UI 154-380 million), Shigella spp. (188 million; 95% UI 94-379 million) and Giardia lamblia (179 million; 95% UI 125-263); the largest number of deaths were caused by norovirus (213,515; 95% UI 171,783-266,561), enteropathogenic E. coli (121,455; 95% UI 103,657-143,348), ETEC (73,041; 95% UI 55,474-96,984) and Shigella (64,993; 95% UI 48,966-92,357). There were marked regional differences in incidence and mortality for these nine diseases. Nearly 40% of cases and 43% of deaths caused by these nine diarrhoeal diseases occurred in children under five years of age.Diarrhoeal diseases caused by these nine pathogens are responsible for a large disease burden, particularly in children. These aetiology-specific burden estimates can inform efforts to reduce diarrhoeal diseases caused by these nine pathogens commonly transmitted through foods.
| S-EPMC4668836 | biostudies-literature
Project description:BackgroundThe increasing numbers of people living with HIV (PLHIV) who are receiving antiretroviral therapy (ART) have near normal life-expectancy, resulting in more people living with HIV over the age of 50 years (PLHIV50+). Estimates of the number of PLHIV50+ are needed for the development of tailored therapeutic and prevention interventions at country, regional and global level.MethodsThe AIDS Impact Module of the Spectrum software was used to compute the numbers of PLHIV, new infections, and AIDS-related deaths for PLHIV50+ for the years 2000-2016. Projections until 2020 were calculated based on an assumed ART scale-up to 81% coverage by 2020, consistent with the UNAIDS 90-90-90 treatment targets.ResultsGlobally, there were 5.7 million [4.7 million- 6.6 million] PLHIV50+ in 2016. The proportion of PLHIV50+ increased substantially from 8% in 2000 to 16% in 2016 and is expected to increase to 21% by 2020. In 2016, 80% of PLHIV50+ lived in low- and middle-income countries (LMICs), with Eastern and Southern Africa containing the largest number of PLHIV50+. While the proportion of PLHIV50+ was greater in high income countries, LMICs have higher numbers of PLHIV50+ that are expected to continue to increase by 2020.ConclusionsThe number of PLHIV50+ has increased dramatically since 2000 and this is expected to continue by 2020, especially in LMICs. HIV prevention campaigns, testing and treatment programs should also focus on the specific needs of PLHIV50+. Integrated health and social services should be developed to cater for the changing physical, psychological and social needs of PLHIV50+, many of whom will need to use HIV and non-HIV services.
| S-EPMC6264840 | biostudies-literature