Enteroviral infection has been long-associated with type 1 diabetes in been linked with enteroviral infection but a causal relationship has proven hard to establish. Type 1 diabetes arises from a complex interaction between genetic, enteroviruses: a critical review from a public-health perspective. This in turn might act as an exacerbating and difficult to trace influence. infections and type 1 diabetes (T1D) focusing on the following research questions: 1) The .. Relationship between the epidemiology of enterovirus infections .. conditions and a low standard of hygiene compared to developed countries, where Enterovirus infections are often difficult to diagnose based solely on clinical.
About 5 percent of people with diabetes have type 1. She's a researcher at the University of Tampere in Finland. The researchers stressed that this study wasn't designed to find a cause-and-effect relationship.
He's a professor of virology at the University of Tampere. The researchers suspect that at least half of type 1 diabetes cases might be linked to enteroviruses.
The study included "case" children who tested positive for multiple islet autoantibodies, and similar children without the autoantibodies to serve as a control group. Researchers tested more than 1, stool samples from the case children, and more than 3, from the control group. They found infections in case children and in the control group. The study team also noted that the excess of infections in the case children occurred more than 12 months before the first positive autoantibody was seen.
There's no known way to prevent enteroviruses -- except for polio and enterovirus 71, for which there are vaccines, the study authors said.
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But, this study, along with past evidence, suggest that vaccines for other enteroviruses might help reduce the incidence of type 1 diabetes. She said it's "exciting to see what this study adds to what's long been thought to contribute to type 1 diabetes in at least a subset of people. It may not always be enteroviral infections," she said. Dunne said a vaccine would need to be given "somewhere between birth and 12 months," because of the lag time seen between infection and the development of autoantibodies.
She and the study authors said that parents shouldn't be overly concerned if their child gets sick with an enterovirus. Most youngsters who get the infections don't go on to get type 1 diabetes. There's no way to prevent your kids from getting enteroviruses," Dunne said. Many studies suggest that the gastrointestinal tract GIT has an important role in the pathogenesis of T1D .
Intestinal microfloras, permeability of mucosal barrier, and immunity have all been linked to T1D . Environmental factors can modify the normal gut microflora or they can change the gut cytokine milieu, including gastrointestinal tract infections . This theory implies that local virus infection in the pancreatic islets maintains inflammation and creates proinflammatory milieu leading to activation of antigen-presenting cells and autoreactive lymphocytes .
Studies with isolated human pancreatic islets cells of Langerhans have demonstrated that the effect of virus replication in the islet cells is serotype and strain-dependent, as some of the viruses cause severe morphological changes and cell death, as well as functional impairment, whereas some serotypes and isolates are less destructive .
Several genes that are associated with T1D are known to have a role in antiviral immune responses. The Human Leukocyte Antigen genes that modulate the risk of T1D are associated with immune response against certain viruses including EVs  and can also modulate the course of virus infections . However, findings of immune cross-reactivity are conflicting. Further suggestive evidence of acute versus persistent EV infection comes from cytokine studies in the newly diagnosed T1D patients.
Enteroviruses, type 1 diabetes and hygiene: a complex relationship.
These form part of the early innate response to viral infection, and high levels therefore suggest recent infection . Prevention and treatment of enteroviruses infections Most people infected with EVs do not have clinical symptoms, but can still spread the virus to other people. This makes it difficult to prevent them from spreading . However, the best way to protect people from EV infections is to wash your hands often with water and soap, especially after using the toilet and changing diapers, and to avoid close contact, such as touching and shaking hands, with people who are sick.
In addition, cleaning and disinfecting of frequently touched surfaces is very important in minimizing risk of contracting EVs from inanimate objects . Even though there is no specific treatment for EV infection, as with other viral pathogens, there are several steps in the replication cycle of the EVs that are potential targets in antiviral therapy.
Cell susceptibility, viral attachment, viral uncoating, viral RNA replication, and viral protein synthesis have all been studied as targets of antipicornaviral compounds .
As the primary mechanism of EV clearance is by humoral immunity, patients who lack antibody because of congenital or acquired immunodeficiencies are uniquely susceptible to infections with the EVs . Similarly, normal neonates are at a high risk for severe EV disease because of a relative deficiency of EV antibodies .
Immune serum globulin has been used prophylactically and therapeutically against the EVs in two clinical settings: The high mortality rate of this disease, coupled with the known association of severe EVs associated diseases such as autoimmunity, has prompted numerous investigators to administer antibody preparations to neonates with EV sepsis . There is currently no licensed vaccine to protect people from EV infection.
However, there are vaccine candidates for EV-A71 in clinical trials.
Common Virus May Have Ties to Type 1 Diabetes
The inactivated EV-A71 vaccine is considered the safest viral vaccine . Up to date, five organizations have completed preclinical studies to develop an inactivated vaccine that is at different phases of clinical trials .
Three of the companies are from China, whereas the other two are from Taiwan and Singapore, respectively. The three companies conducted randomized, double-blind, placebo-controlled, multicenter trials involving over 30 healthy children. Each candidate received two intramuscular doses of vaccine or placebo within a span of 28 days apart . Sinovac reported that their inactivated vaccine efficacy was In addition, the anti-EV-A71 neutralizing titer of 1: Diagnosis of enteroviruses in diabetic patients Specific diagnosis of EV infections demands detection in samples collected from the patient, as clinical signs are not sufficiently specific because of the diversity of host responses and the large number of different EV serotypes.
Diagnosis involves both clinical and epidemiological features . The main methods used to detect EVs include viral culture, serology immunofluorescence, and nucleic acid amplification tests. Using two techniques in combination might be a good option to identify EVs and to associate it with the development of T1D, particularly in children .
In addition to epidemiological studies, an association between EVs and T1D has been evaluated by searching for EVs in the pancreatic tissue of T1D patients. Obviously, in case of viral persistence, the virus should be detectable for longer periods of time and at different stages of the diabetic process assuming that enough virus proteins and RNA are produced . Serological assays using EV-specific immunoglobulin M and immunoglobulin G have limited application in diagnosis of EV infection.
This is because EV serology has poor technical indices of antibody detection and possibility of cross-reaction with similar viruses such as adenoviruses and reovirus . Recently, the possible cross-reactivity of antibodies used in IHC with pancreatic islet cell proteins has been studied extensively .
Altogether, this antibodies seem to react with several EV types. In addition, it may also recognize some host proteins if used in nonoptimal conditions, and therefore the staining conditions should be optimized for different tissues and the presence of the virus should be confirmed by other methods . With the advent of molecular techniques, identification has become easier, which has helped both patient diagnosis and epidemiological studies.
In many countries, T1D has become a crucial noncommunicable disease that has been linked to several EV infections. PCR studies of viremia before or around the time of T1D diagnosis is quite significant, but is difficult to interpret. However, cohort prospective studies from birth using improved investigation technologies will eventually solve some of these issues.