Transmissible Infectious Diseases Research Articles

The expanding role of immunopharmacology: IUPHAR Review 16.

Drugs targeting the immune system such as corticosteroids, antihistamines and immunosuppressants have been widely exploited in the treatment of inflammatory, allergic and autoimmune disorders during the second half of the 20th century. The recent advances in immunopharmacological research have made available new classes of clinically relevant drugs. These comprise protein kinase inhibitors and biologics, such as monoclonal antibodies, that selectively modulate the immune response not only in cancer and autoimmunity but also in a number of other human pathologies. Likewise, more effective vaccines utilizing novel antigens and adjuvants are valuable tools for the prevention of transmissible infectious diseases and for allergen-specific immunotherapy. Consequently, immunopharmacology is presently considered as one of the expanding fields of pharmacology. Immunopharmacology addresses the selective regulation of immune responses and aims to uncover and exploit beneficial therapeutic options for typical and non-typical immune system-driven unmet clinical needs. While in the near future a number of new agents will be introduced, improving the effectiveness and safety of those currently in use is imperative for all researchers and clinicians working in the fields of immunology, pharmacology and drug discovery. The newly formed ImmuPhar (http://iuphar.us/index.php/sections-subcoms/immunopharmacology) is the Immunopharmacology Section of the International Union of Basic and Clinical Pharmacology (IUPHAR, http://iuphar.us/). ImmuPhar provides a unique international expert-lead platform that aims to dissect and promote the growing understanding of immune (patho)physiology. Moreover, it challenges the identification and validation of drug targets and lead candidates for the treatment of many forms of debilitating disorders, including, among others, cancer, allergies, autoimmune and metabolic diseases.

Controlling infectious disease through the targeted manipulation of contact network structure

Individuals in human and animal populations are linked through dynamic contact networks with characteristic structural features that drive the epidemiology of directly transmissible infectious diseases. Using animal movement data from the British cattle industry as an example, this analysis explores whether disease dynamics can be altered by placing targeted restrictions on contact formation to reconfigure network topology. This was accomplished using a simple network generation algorithm that combined configuration wiring with stochastic block modelling techniques to preserve the weighted in- and out-degree of individual nodes (farms) as well as key demographic characteristics of the individual network connections (movement date, livestock market, and animal production type). We then tested a control strategy based on introducing additional constraints into the network generation algorithm to prevent farms with a high in-degree from selling cattle to farms with a high out-degree as these particular network connections are predicted to have a disproportionately strong role in spreading disease. Results from simple dynamic disease simulation models predicted significantly lower endemic disease prevalences on the trade restricted networks compared to the baseline generated networks. As expected, the relative magnitude of the predicted changes in endemic prevalence was greater for diseases with short infectious periods and low transmission probabilities. Overall, our study findings demonstrate that there is significant potential for controlling multiple infectious diseases simultaneously by manipulating networks to have more epidemiologically favourable topological configurations. Further research is needed to determine whether the economic and social benefits of controlling disease can justify the costs of restricting contact formation.

Re-thinking the ethics of dual-use research of concern on transmissible pathogens

Rapid acceleration in the science of genetic engineering of infectious diseases has outpaced legal and ethical frameworks for dealing with such research. Dual-use research of concern (DURC), which can be used for good or for harm, raises new questions about potential harm to human beings which have not traditionally been considered by medical research ethics committees, and may require us to revise and standardize ethical guidelines worldwide for the conduct of such research. The weighing of harm versus benefit of research as traditionally considered on an individual level needs to be considered on a population level for infectious diseases DURC, and on a global level due to the potential for transmissible infections to cause a pandemic, thus affecting people in places far from where the research was conducted. The harm of such research could result from either laboratory accidents or bioterrorism. As an example, engineered organisms such as influenza could result in an unnatural pandemic, affecting and harming people who were never informed of the research nor consented to it. The debate to date has been held among medical researchers and has been focused on the rights of researchers and scientific freedom. The community is also a stakeholder with rights, and DURC done in one country could cause harm to people in other countries who were never included in the debate. The first requirement is to inform and engage the public as a stakeholder in such research, and to make deliberations about DURC public and transparent. Secondly, governance structures and guidelines are not uniform internationally, and only some institutions and countries have specific DURC policies, none of which are enforceable. Consistent international guidelines and uniform, enforceable global governance models need to be developed for medical research ethics committees around potential population harm and benefit of DURC. Finally, researchers should be required to quantify potential population risks and benefits of DURC before it is approved. Models for quantifying risk–benefit equations could be drawn from health economics, with the onus on researchers to demonstrate that potential benefit outweighs potential harm. These would be positive steps towards protecting the interests and rights of all potentially affected populations in the case of transmissible infectious disease DURC. Past quantum changes in medical research governance such as mandatory registration of clinical trials show that major changes in research culture can be achieved. Current systems leave community stakeholders vulnerable to potential harms of infectious diseases DURC, and need to be addressed in a consistent and comprehensive manner internationally to ensure ethical obligations are met.

Helicobacter pylori and its orodental implications: A review

Helicobacter pylori (H. pylori) is a Gram-negative, microaerophillic, spiral bacterium. The prevalence of H. pylori infection was estimated to range from 40% to 80% and it varies widely. The advancement of biochemical techniques provided new information about the pathogenicity and virulence factors of H. pylori indicating a complex interaction of bacterial and host factors for infection by H. pylori. It is regarded as a serious and transmissible infectious disease linked to duodenal and gastric ulcers, gastric carcinoma, and also as a cofactor in the recurrence of aphthous ulceration. This article focuses on the pathogenesis, disease associations, and the orodental implications of H. pylori.

Enfermedades infecciosas en población adulta extranjera ingresada en un hospital general

IntroductionTo determine the infectious diseases (ID) that led to hospital admission of the foreign population>14 years. Material and methodsA retrospective study of foreign patients admitted to hospital (2000-2012). ResultsA total of 3,087 foreigners were admitted with infectious diseases. Of these, 73.6% were from low income countries, and 26.4% from high income countries. Most of them (86.9%) were admitted with common ID, 11.8% with transmissible ID, and 1.6% with tropical ID. Tropical ID and transmissible ID were higher in patients from low income countries (14.7%) than from high income countries (9.7%, p<0.001). The main tropical ID was malaria (74%). The main transmissible ID were tuberculosis (40.3%), hepatitis (27.8%), and HIV/AIDS (27.5%). ConclusionCommon ID were the main reason for admission in foreign population.

Early Childhood Caries - A Continuing Oral Health Problem: A Review

Early Childhood Caries (ECC) is a chronic, transmissible infectious disease affecting the primary teeth. The etiology of the condition is a combination of factors including frequent consumption of fermentable carbohydrates as liquids, especially when the baby is sleeping, with on-demand breast- or bottle-feeding. Other factors include oral colonization by cariogenic bacteria (especially mutans streptococci), poor oral hygiene and poor parenting. It is the most common chronic disease among children. The prevalence of ECC in infants and preschool children has been reported to vary between 3% and 94% world-wide. ECC can result in considerable suffering, pain, disfigurement and frequently compromises future dentition. This ultimately leads to a reduction in the quality of life of affected children. This paper provides an updated review of ECC. Its terminology, etiology, prevalence, clinical picture, complications and management are critically discussed and a solution to the continuing problem of ECC is suggested. Keywords: Cellulitis, diet, Early Childhood Caries (ECC), lactobacilli (LB), mutans streptococci (MS), prevalence, prevention, tooth brushing.

Transmissible Infectious Diseases in Internationally Adopted Children

Transmissible Infectious Diseases in Internationally Adopted Children

The infection tree of global epidemics

The spreading of transmissible infectious diseases is inevitably entangled with the dynamics of human population. Humans are the carrier of the pathogen, and the large-scale travel and commuting patterns that govern the mobility of modern societies are defining how epidemics and pandemics travel across the world. For a long time, the development of quantitative spatially explicit models able to shed light on the global dynamics of pandemic has been limited by the lack of detailed data on human mobility. In the last 10 years, however, these limits have been lifted by the increasing availability of data generated by new information technologies, thus triggering the development of computational (microsimulation) models working at a level of single individuals in spatially extended regions of the world. Microsimulations can provide information at very detailed spatial resolutions and down to the level of single individuals. In addition, computational implementations explicitly account for stochasticity, allowing the study of multiple realizations of epidemics with the same parameters' distribution. While on the one hand these capabilities represent the richness of microsimulation methods, on the other hand they face us with a huge amount of information that requires the use of specific data reduction methods and visual analytics.

Mother's knowledge and practice regarding oral Hygiene and challenges in the prevention of dental caries of under-five children in an urban resettlement colony

Background: Dental carries is transmissible infectious disease and mother is the major primary source of infection for their children. Aims & Objective: To assess knowledge and practice of mothers of under-five children regarding dental caries. Material and Methods: 140 mothers having < 5 years old children selected through simple random sampling were interviewed using semi-structured schedule to assess the knowledge of oral health to prevent dental caries. Results: In the survey, 73.5% mothers knew about avoiding consumption of sweets/sweet fast foods/sugar beverages. A larger proportion of literate mothers were aware of regular cleaning of mouth, necessity of cleaning mouth after each feeding, sweets / sweet fast food & unclean mouth causes caries (p>0.05). They offers sweet/sweet fast food / sugar beverages more frequently, use toothpaste and brush for cleaning mouth for their children’s (p=0.010, p=0.008). A larger proportion of mothers who had an income > 3000 `/month were aware of sweets / sweet fast food & unclean mouth causes caries, necessity of regular cleaning after each feeding (p>0.05). But in spite of greater awareness of mothers a significantly lesser proportion of their children used toothpaste while brushing, do self-brushing and assisted brushing (p=00.007, 0.025, 0.022). An age group of >24 years and income > 3000 `/month were the predictors of good oral hygiene practice by mothers. Conclusion: Mothers of the study area had basic knowledge of caries prevention. However, their theoretical knowledge has been not fully reflected in the way they cared for their children\'s teeth.

Seroprevalence of Transfusion Transmissible Infections (TTIs) among blood donors in a tertiary care hospital, central India: A prospective study

Background: Blood transfusion having some risks of transfusion transmissible infections (TTIs) in the recipients especially when blood is collected during window period. In Africa, about 10-15% of human immunodeficiency virus (HIV) transmission had been related to blood transfusions. Aims: The aim of this study is to present the prevalence of TTIs among the apparently healthy donors, both voluntary as well as replacement donors. Settings and Design: This was a prospective study, carried out in a blood bank attached to a tertiary care hospital, Central India. Materials and Methods: All blood bags collected from these blood donors during the study period were screened for TTIs like hepatitis B surface antigen (HBsAg; Hepalisa, J. Mitra), anti-HIV antibodies (HIV Ab; HIV 3rd generation kit for detection of antibodies to HIV1 and HIV2, J. Mitra), anti-hepatitis C virus antibodies (HCV Ab; MicroELISA 3rd generation, J. Mitra), and Venereal Diseases Research Laboratory (VDRL) reactivity (Carbogen kit, Tulip Diagnostics). Serum were separated from all blood bags and serological test was performed according to the instructions provided by the manufacturers of respective kit. All seroreactive blood bags were considered as positive for TTIs and the blood bags were discarded. Statistical Analysis: A total of 10,582 blood donors were selected for blood donation after clinical history and brief medical examination by medical officer. Blood bags collected from them were screened for TTIs. Among the total blood bags screened, 273 (2.57%) were found positive for transfusion transmissible infectious diseases. Results: Among TTIs, the most common infection was hepatitis B followed by HIV infection in our study. Prevalence of coinfection in our study was very low (0.01%). Voluntary donations have low seroreactivity (2.40%) for TTIs as compared to replacement donations (3.20%). Conclusions: Multiple infections have a very small but definite risk to the recipients, recieving blood and blood products. Hepatitis B was the most common infection in our study. The incidence of coinfection was very low in our study. Prevalence of TTIs was more among replacement donors as compared to the voluntary donors. So, it is possible to improve the safety of blood and blood product by the promotion of voluntary donation, selection of low-risk donors, and use of highly sensitive laboratory screening test.

Analysis of reasons for discarding blood and blood components in a blood bank of tertiary care hospital in central India: A prospective study

Background: Many modern surgical procedures could not be carried out without the use of blood. There are no substitutes for human blood. Thus, proper utilization of blood is necessary with minimal wasting. Materials and Methods: A total of 10,582 donors donated blood during the study period of 19 months in blood bank of a tertiary care hospital, central India from 1 st of November 2009 to 31 st May 2011, which were screened. Results: A total of 346 whole blood bags were discarded. Out of these 346 blood bags, 257 (74.30%) were discarded because of seropositivity for transfusion transmissible infectious diseases. A total of 542 blood components were discarded against 3702 blood components prepared during the study period. Among blood components discarded, most common units were platelets. The most common cause of discarding the blood components was expiry of date due to non-utilization (87.00%). Conclusion: A properly conducted donor interview, notification of permanently deferred donors will help in discarding less number of bags from collected units. Similarly, properly implemented blood transfusion policies will also help in discarding less number of blood bags due to expiry. These discarded bags, because they are unutilized are both financially as well as socially harmful to the blood bank.

Diet and the microbial aetiology of dental caries: new paradigms

To compare the effect of 40 seconds versus 2 minutes brushing on saliva and dental biofilm fluid fluoride in children ages 4-5 years over 1 hour. This was a single-blind, cross-over, randomised, two-period clinical study in healthy children. Three days before the start of each treatment subjects received a thorough brushing and then refrained from all oral hygiene procedures. At treatment visits, after collecting baseline biofilm and saliva samples, staff brushed the occlusal surfaces of the subject's posterior teeth with a pea-sized amount (0.25 g) of NaF/silica toothpaste for the randomised time. Samples were taken at 5 minutes, 15 minutes, 30 minutes and 60 minutes after brushing and analysed for fluoride using a microanalytical methodology. There was a minimum 4-day washout period between treatments. Log changes from baseline biofilm fluid and saliva fluoride were statistically significant (P < 0.05) for both brushing times at all post-brushing time-points [except 60 minutes saliva where P = 0.06 (t-test)]. Statistically significantly greater ln-AUC (area under the curve) was found for biofilm fluid and salivary fluoride after brushing for 2 minutes compared with brushing for 40 seconds over the 1-hour test period. There was a statistically significantly higher concentration of fluoride in the log change from baseline saliva levels after 5, 15, 30 and 60 minutes for the 2-minute brushing time compared with 40 seconds brushing time. There was no statistically significant difference in concentration of log change from baseline fluoride levels in biofilm fluid at each individual time-point (5, 15, 30 and 60 minutes) for the 2-minute brushing time compared with the 40-second brushing time, but significant differences were observed for 15, 30 and 60 minutes in favour of 2-minute brushing time when log biofilm fluid value was analysed. The findings provide further evidence for the benefits of increased duration of brushing with respect to fluoride delivery.

Ex VivoExpansion of Hematopoietic Stem- and Progenitor Cells from Cord Blood in Coculture with Mesenchymal Stroma Cells from Amnion, Chorion, Wharton's Jelly, Amniotic Fluid, Cord Blood, and Bone Marrow

In most cases, the amount of hematopoietic stem and progenitor cells (HSPCs) in a single cord blood (CB) unit is not sufficient for allogenic transplantation of adults. Therefore, two CB units are usually required. The ex vivo expansion of HSPCs from CB in coculture with mesenchymal stroma cells (MSCs) might be an alternative. It was investigated, whether bone marrow-derived MSCs, which have to be obtained in an invasive procedure, introduce a further donor and increases the risk of transmissible infectious diseases for the patient can be replaced by MSCs from amnion, chorion, Wharton's jelly, amniotic fluid, and CB, which can be isolated from placental tissue which is readily available when CB is sampled. In a two-step ex vivo coculture mononuclear cells from cryopreserved CB were cultured with different MSC-feederlayers in a medium supplemented with cytokines (stem cell factor, thrombopoietin [TPO], and granulocyte colony-stimulating factor). Expansion rates were analyzed as well, by long-term culture-initiating cell (LTC-IC) and colony-forming unit (CFU) assays, as by measuring CD34(+)- and CD45(+)-cells. Due to the comparably low number of 5×10(2) to 1×10(4) CD34(+)-cells per cm(2) MSC-monolayer, we observed comparably high expansion rates from 80 to 391,000 for CFU, 70 to 313,000 for CD34(+)-, and 200 to 352,000 for CD45(+)-cells. Expansion of LTC-IC was partly observed. Compared to the literature, we found a better expansion rate of CD34(+)-cells with MSCs from all different sources. This is probably due to the comparably low number of 5×10(2) to 1×10 CD34(+)-cells per cm(2) MSC-monolayer we used. Comparably, high expansion rates were observed from 80 to 391,000 for CFUs, 70 to 313,000 for CD34(+)-, and 200 to 352,000 for CD45(+)-cells. However, the expansion of CD34(+)-cells was significantly more effective with MSCs from bone marrow compared to MSCs from amnion, chorion, and Wharton's jelly. The comparison of MSCs from bone marrow with MSCs from CB and amniotic fluid showed no significant difference. We conclude that MSCs from placental tissues might be useful in the expansion of HSPCs, at least if low numbers of CD34(+)-cells per cm(2) MSC-monolayer and a high TPO concentration are implemented in the expansion culture.

Evaluation of syndromic algorithms for detecting patients with potentially transmissible infectious diseases based on computerised emergency-department data

BackgroundThe objective of this study was to ascertain the performance of syndromic algorithms for the early detection of patients in healthcare facilities who have potentially transmissible infectious diseases, using computerised emergency department (ED) data.MethodsA retrospective cohort in an 810-bed University of Lyon hospital in France was analysed. Adults who were admitted to the ED and hospitalised between June 1, 2007, and March 31, 2010 were included (N=10895). Different algorithms were built to detect patients with infectious respiratory, cutaneous or gastrointestinal syndromes. The performance parameters of these algorithms were assessed with regard to the capacity of our infection-control team to investigate the detected cases.ResultsFor respiratory syndromes, the sensitivity of the detection algorithms was 82.70%, and the specificity was 82.37%. For cutaneous syndromes, the sensitivity of the detection algorithms was 78.08%, and the specificity was 95.93%. For gastrointestinal syndromes, the sensitivity of the detection algorithms was 79.41%, and the specificity was 81.97%.ConclusionsThis assessment permitted us to detect patients with potentially transmissible infectious diseases, while striking a reasonable balance between true positives and false positives, for both respiratory and cutaneous syndromes. The algorithms for gastrointestinal syndromes were not specific enough for routine use, because they generated a large number of false positives relative to the number of infected patients. Detection of patients with potentially transmissible infectious diseases will enable us to take precautions to prevent transmission as soon as these patients come in contact with healthcare facilities.

Management of mammalian bites and venomous stings in primary care

Primary care physicians should be familiar with procedure of diagnosis, treatment and triage of patients as well as prevention of transmissible diseases in animal bites and poisonous stings. The most frequent wounds from mammalian bites are of dogs, then cats, humans and rodents rarely and sporadically other domestic and wild animals. Treatment should start with primary wound care. Most wound bites have a small infection risk and routine prophylactic antibiotic is not recommended. Antibiotics useful in wound infections are amoxicillin plus clavulanic acid, ciprofloxacin, doxycycline, clindamycin, metronidazole and trimethoprim plus sulfamethoxazole. In our country, long-nosed viper and common European adder are only important species of poisonous snakes. In addition to local symptoms and hemorrhagic shock, induced by coagulopathy, other syndromes of systemic intoxication after snakebite are: neurotoxicity, myotoxicity, nephrotoxicity and early cardiovascular collapse. First aid consists of the rest and broad, compressive immobilization of affected limb. Routine use of snake antivenom is not recommended and it is given primarily during an intoxication or severe, progressive local damage. Insect bites cause allergic reactions, envenomation or transmissible infectious diseases. Local reactions in hymenoptera stings are limited and occur in non-allergic people. Mass sting events occur only in cases of numerous insect bites, usually hundreds to thousands of honey bee, tens and hundreds of wasps but a few of hornets. Treatment of severe local reaction involves limb elevation, prescription of anti-allergic drugs and anaphylactic shock care. General practitioner, according to current health regulations, must consider tetanus and rabies prophylaxis and apply them, if necessary.

The role of informed consent in tuberculosis testing and screening

In December 2010, the World Health Organization (WHO) endorsed the use of a new DNA-based test for tuberculosis (TB), the Gene Xpert [1]. This test is expected to revolutionise the care of TB and, especially, multidrug-resistant (MDR)-TB, by providing accurate diagnoses in less than 2 h [2]. As healthcare professionals begin to incorporate rapid TB testing into clinical practice, questions about the need for informed consent will inevitably arise. Yet, despite decades of debate about informed consent to HIV testing and screening [3], informed consent to TB testing and screening has received virtually no discussion in the ethical or legal literature. In this editorial, we argue that, in most situations, TB testing and screening does not require a specific informed consent process, but that patients should be notified about testing and given the opportunity to object. If an objection is raised, the burden should be on those proposing coercive testing to show that the expected public health benefits are sufficient to justify overriding the individual's choice. We conclude by identifying limited circumstances in which specific informed consent to TB testing should be required. When the HIV diagnostic test was first developed, many jurisdictions enacted laws requiring written informed consent to testing [3]. The rationale was that HIV was untreatable, and individuals who tested positive faced a significant risk of stigmatisation and discrimination [3]. Moreover, because HIV was not transmissible by casual contact, the public health rationale for facilitating testing was weaker than with more easily transmissible infectious diseases. As HIV has become more treatable and less stigmatised, policy makers have begun to shift their approach. In 2006, the US Centers for Disease Control and Prevention (USCDC) recommended that HIV testing should routinely be performed in all healthcare settings [4 …

The re-emergence of measles in developed countries: Time to develop the next-generation measles vaccines?

The re-emergence of measles in developed countries: Time to develop the next-generation measles vaccines?

Safety of liver transplantation with chagas disease-seropositive donors for seronegative recipients

The shortage of organs for transplantation has prompted the investigation of extended criteria donors, such as donors with transmissible infectious diseases. Here we report our recent experience with liver transplantation using organs from donors who were serologically positive for Chagas disease. We also provide a review of the literature and emphasize donor screening and preventive measures.

In vitro production of red blood cells

Blood transfusion is a mainstay of modern clinical medicine. However, a number of fundamental problems persist, including insufficiency of supply, the threat of transfusion transmissible infectious disease and the problem of immune incompatibility. It would be extremely valuable, therefore, to develop a potentially limitless, infection free, immune neutral source of erythrocytes for transfusion. Human embryonic stem cells (hESC), have potentially limitless proliferative capacity and the potential to differentiate into the majority of adult cell types including erythrocytes. A number of barriers to the development of clinical cellular therapeutics from hESC have been posited, including HLA incompatibility between donor and recipient, difficulties in defining optimal cell phenotype and function in vitro and the fact that most tissues consist of complex three-dimensional matrices of cells. Many or most of these problems are circumvented in the generation of erythrocytes and group O RhD negative Kell negative blood would be compatible with the majority of recipients. Red cell transfusion is therefore an attractive goal for pluripotent stem cell derived therapeutics. Much progress has been made however, a number of challenges remain including scale up, ensuring clinical effectiveness and product safety.

Seroepidemiological survey of transmissible infectious diseases in a portuguese prison establishment

A cross-sectional study was conducted in 151 (71.6%) of 211 male inmates of a regional Portuguese prison in order to establish the seroprevalence for viral hepatitis (HAV, HBV, HCV), human immunodeficiency virus (HIV), syphilis and herpes simplex virus (HSV-1 and HSV-2) and to analyze some psychosocial and criminal characteristics. Mean age was 34 years. Anti-HAV was positive in 69.5% (n = 105) and in 34.4% (n = 52) for anti-HCV. One (0.7%) person had HBsAg and 29 (19.2%) had laboratory markers of past HBV infection. Non-immune inmates for HBV were 40.4% (n = 61). Syphilis was diagnosed in 6.0% (n = 9). The rate of HIV infection was 6.6% (n = 10; all HIV-1). The seropositivity of HSV-2 was 19.9% (n = 30) and of HSV-1 was 82.1% (n = 124). Alcohol dependence was reported by 26.5% (n = 40). Excluding tobacco and prescription medication, 73.5% (n = 111) reported drug use in prison. The most commonly used drugs were: cannabis (100%; n = 111) followed by heroin (56.7%; n = 63). Anti-HCV rate was noteworthy. The HIV infection rate (6.6%) in this regional prison is at least 13 to 22 times greater than in general population. As the inmate return to the community increases the risk of disease exposure for the general population, early detection and counseling is urgently needed for prisoners.