In some elimination settings, at a given time many malaria infections either are asymptomatic or cause only minor symptoms (Lindblade and others 2013). Passive surveillance misses those individuals who act as parasite reservoirs that are infectious to mosquitoes, causing onward transmission (Sturrock and others 2013). A substantial proportion of infections may also be subpatent or submicroscopic, that is, the density of parasites is lower than the threshold for detection by microscopy or rapid diagnostic tests. These infections account for 20 percent to 50 percent of all transmission occurrences in low-endemic settings (Mosha and others 2013; Okell and others 2012). Draining this asymptomatic reservoir is thus important for elimination. There is, however, growing certitude that curing all symptomatic infections will automatically shrink this asymptomatic reservoir.
Interest in the empiric administration of a therapeutic antimalarial regimen to an entire population at the same time, otherwise known as mass drug administration (MDA), has recently been renewed. Proactive MDA has been successfully deployed against several infectious diseases, including lymphatic filariasis, onchocerciasis, schistosomiasis (Hotez 2009), and malaria (Bruce-Chwatt 1959; Newby and others 2015; Poirot and others 2013). The goal is to interrupt transmission by treating all parasitemia in the population. MDA can potentially reduce malaria mortality and morbidity through its direct therapeutic effect on individuals who receive a treatment dose of antimalarials. It also can reduce transmission rates by reducing parasitemia prevalence and interrupting various stages of the parasite lifecycle, and it can inhibit the sporogonic cycle in the mosquito, reducing its vectorial capacity. If every member of a given population were treated by antimalarial MDA, the prevalence of asexual parasites in the population would immediately decline.
Programs can also be integrated, making disease programs more efficient as well as creating a platform for mobilizing resources, even if malaria is no longer considered a priority. For example, in Singapore, integrating dengue and malaria surveillance facilitated interagency collaboration and reduced transmission of both diseases (Luckhart and others 2010). When transmission decreases and eventually ceases, costs are likely to decline and eventually stabilize as efforts turn to preventing reintroduction primarily through surveillance, vector control, and emergency response. Private out-of-pocket expenditures are also likely to become negligible as the number of cases declines. Two studies (figure 12.2) with empirical data on expenditures over multiple programmatic phases found that expenditures declined when moving from elimination to prevention-of-reintroduction (Abeyasinghe and others 2012; Smith Gueye and others 2014). A study in Sri Lanka estimated the financial cost of prevention of reintroduction activities to cost US$0.37 in 2014 (Shretta and others 2016), less than a quarter of the expenditures in previous years (Abeyasinghe and others 2012).
Infectious diseases are the leading cause of death globally, particularly among children and young adults. The spread of new pathogens and the threat of antimicrobial resistance pose particular challenges in combating these diseases. Major Infectious Diseases identifies feasible, cost-effective packages of interventions and strategies across delivery platforms to prevent and treat HIV/AIDS, other sexually transmitted infections, tuberculosis, malaria, adult febrile illness, viral hepatitis, and neglected tropical diseases.
Emerging infectious diseases are a major threat to health: AIDS, SARS, drug-resistant bacteria and Ebola virus are among the more recent examples. By identifying emerging disease 'hotspots', the thinking goes, it should be possible to spot health risks at an early stage and prepare containment strategies. An analysis of over 300 examples of disease emerging between 1940 and 2004 suggests that these hotspots can be accurately mapped based on socio-economic, environmental and ecological factors. The data show that the surveillance effort, and much current research spending, is concentrated in developed economies, yet the risk maps point to developing countries as the more likely source of new diseases.
Colonization rates decrease with increasing age [140, 147, 151, 152]. The prevalence of asymptomatic colonization with C. difficile is still elevated in the second year of life, although to a lesser degree than in infants [139, 153, 154]. Therefore, testing in this population should also be avoided unless other infectious and noninfectious causes of diarrhea have been excluded. Consistent with the epidemiology of CDI in infants and young children, the NHSN does not permit reporting of CDI from newborn nurseries and neonatal ICU locations. Additionally, public reporting of cases in children
Determining the optimal number of episodes of diarrhea that justifies the need for CDI testing depends on the likelihood of infection (high vs low CDI rates), potential confounders (underlying diseases and/or medical or surgical interventions that increase the chance of iatrogenic diarrhea), risk factors for CDI, and the chosen testing methods (high vs low specificity/predictive value methods).
FMT has been well accepted by patients and represents a viable alternative treatment approach to an increasing clinical problem. Judged by the published literature, FMT appears to be safe in the short term [359, 367, 372, 373] and mild to moderate posttreatment adverse events are for the most part self-limited . A recent retrospective multicenter case series report of 80 immunocompromised patients concluded that FMT was safe and well tolerated, although they included a heterogenous group of conditions . Reported infectious complications directly attributed to the instillation of donor feces has so far been limited to 2 patients who developed norovirus gastroenteritis after FMT for treatment of CDI despite use of asymptomatic donors and lack of sick contacts . Physical complications from the FMT instillation procedure (upper gastrointestinal bleed after nasogastric tube insertion, colon perforation during colonoscopy) has been occasionally reported and may occur with the same frequency as when these procedures are performed for gastrointestinal illnesses other than recurrent CDI. Potential unintended long-term infectious and noninfectious consequences of FMT are still unknown in the absence of large-scale controlled trials with sufficient follow-up.
What is the epidemiology of CDI? What is the incubation period of C. difficile? What is the infectious dose of C. difficile? How should hospital rates be risk-adjusted for appropriate interhospital comparisons? Does administration of PPIs increase the risk of CDI and, if so, what is the magnitude of risk? What are the sources for C. difficile transmission in the community? Is exposure to antibiotics (or equivalent agents, such as chemotherapy drugs) required for susceptibility to CDI? If not, what are the antibiotic surrogates or other factors that place patients at risk for CDI, particularly in the community? What is the role of asymptomatic carriers in transmission of C. difficile in the healthcare setting? What are the validated clinical predictors of severe CDI? Can clinical predictors of severe CDI in children be identified? At what age and to what degree is C. difficile pathogenic among infants and young children? How should clinically significant diarrhea be defined in infants and children who are not continent of stool? How should pediatric healthcare facilities conduct surveillance and report rates of C. difficile infection? Should data from infants
Sixty-one articles were selected for inclusion in the review. Most focused on the impacts of residential schooling among First Nations, but some included Métis and Inuit. Physical health outcomes linked to residential schooling included poorer general and self-rated health, increased rates of chronic and infectious diseases. Effects on mental and emotional well-being included mental distress, depression, addictive behaviours and substance mis-use, stress, and suicidal behaviours.
Activated IL-1 is incapable of functioning until recognized by cell surface receptors. The complex contains a motif of GTPase activity and activates GTPase-activating protein and protein kinases [80,81,82]. In contrast, IL-1R2 is thought to reduce the biological response to IL-1. The proximity of the two cytoplasmic domains of IL-1R1 and IL-1R3 is thought to initiate signal transduction by the hydrolysis of GTP. This is followed by c-Jun N-terminal kinase (JNK) and p38 MAP kinase . IRAK and tumor necrosis factor (TNF) receptor-associated factor (TRAF) 6 activate NF-κB, as well as p38, JNKs, extracellular signal-regulated kinases (ERKs), and mitogen-activated protein kinases (MAPKs) . The NF-κB activation pathway is dependent on the Iκ-B kinase (IKK) complex, composed of IKKα, IKKβ, and NF-κB essential modulator (NEMO), via associations with TAK1, TAK2, TRAF2, and TRAF6 in the IL-1R1-signaling pathway . These signals play important roles in both acute and chronic inflammation in various diseases .
Besides the above diseases, numerous inflammatory diseases related to excess IL-1 signaling have also been identified [112,113,114]. For example, high IL-1β levels in humans and mice result in increased Th17-dominant immunopathology, and IL-1β expression was limited to macrophages and neutrophils, which account for a large proportion of the CD45α cells in the cervix upon Chlamydia muridarum infection . Consequently, IL-1β promotes the differentiation of monocytes into conventional dendritic cells (DCs) and M1-like macrophages and supports the proliferation of activated B- lymphocytes and their differentiation into plasma cells [116,117,118]. IL-1 in combination with IL-2 promoted not only the expansion of NK cells but also CD4+ CD8+ T-lymphocytes . IL-1β generated by activated antigen-presenting cells (APCs) induced type 1 immune responses, which produced CTL and led to the polarization of CD4+ T -lymphocytes towards T-helper cell type 1 (Th1) [120, 121]. 2b1af7f3a8