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      The role of infection in miscarriage

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          Abstract

          BACKGROUND

          Miscarriage is the spontaneous loss of a pregnancy before 12 weeks (early miscarriage) or from 12 to 24 weeks (late miscarriage) of gestation. Miscarriage occurs in one in five pregnancies and can have considerable physiological and psychological implications for the patient. It is also associated with significant health care costs. There is evidence that potentially preventable infections may account for up to 15% of early miscarriages and up to 66% of late miscarriages. However, the provision of associated screening and management algorithms is inconsistent for newly pregnant women. Here, we review recent population-based studies on infections that have been shown to be associated with miscarriage.

          METHODS

          Our aim was to examine where the current scientific focus lies with regards to the role of infection in miscarriage. Papers dating from June 2009 with key words ‘miscarriage’ and ‘infection’ or ‘infections’ were identified in PubMed (292 and 327 papers, respectively, on 2 June 2014). Relevant human studies (meta-analyses, case–control studies, cohort studies or case series) were included. Single case reports were excluded. The studies were scored based on the Newcastle – Ottawa Quality Assessment Scale.

          RESULTS

          The association of systemic infections with malaria, brucellosis, cytomegalovirus and human immunodeficiency virus, dengue fever, influenza virus and of vaginal infection with bacterial vaginosis, with increased risk of miscarriage has been demonstrated. Q fever, adeno-associated virus, Bocavirus, Hepatitis C and Mycoplasma genitalium infections do not appear to affect pregnancy outcome. The effects of Chlamydia trachomatis, Toxoplasma gondii, human papillomavirus, herpes simplex virus, parvovirus B19, Hepatitis B and polyomavirus BK infections remain controversial, as some studies indicate increased miscarriage risk and others show no increased risk. The latest data on rubella and syphilis indicate increased antenatal screening worldwide and a decrease in the frequency of their reported associations with pregnancy failure. Though various pathogens have been associated with miscarriage, the mechanism(s) of infection-induced miscarriage are not yet fully elucidated.

          CONCLUSIONS

          Further research is required to clarify whether certain infections do increase miscarriage risk and whether screening of newly pregnant women for treatable infections would improve reproductive outcomes.

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          Most cited references165

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          Differential Roles of TLR2 and TLR4 in Recognition of Gram-Negative and Gram-Positive Bacterial Cell Wall Components

          Toll-like receptor (TLR) 2 and TLR4 are implicated in the recognition of various bacterial cell wall components, such as lipopolysaccharide (LPS). To investigate in vivo roles of TLR2, we generated TLR2-deficient mice. In contrast to LPS unresponsiveness in TLR4-deficient mice, TLR2-deficient mice responded to LPS to the same extent as wild-type mice. TLR2-deficient macrophages were hyporesponsive to several Gram-positive bacterial cell walls as well as Staphylococcus aureus peptidoglycan. TLR4-deficient macrophages lacked the response to Gram-positive lipoteichoic acids. These results demonstrate that TLR2 and TLR4 recognize different bacterial cell wall components in vivo and TLR2 plays a major role in Gram-positive bacterial recognition.
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            Human papillomavirus and cervical cancer.

            Cervical cancer is caused by human papillomavirus infection. Most human papillomavirus infection is harmless and clears spontaneously but persistent infection with high-risk human papillomavirus (especially type 16) can cause cancer of the cervix, vulva, vagina, anus, penis, and oropharynx. The virus exclusively infects epithelium and produces new viral particles only in fully mature epithelial cells. Human papillomavirus disrupts normal cell-cycle control, promoting uncontrolled cell division and the accumulation of genetic damage. Two effective prophylactic vaccines composed of human papillomavirus type 16 and 18, and human papillomavirus type 16, 18, 6, and 11 virus-like particles have been introduced in many developed countries as a primary prevention strategy. Human papillomavirus testing is clinically valuable for secondary prevention in triaging low-grade cytology and as a test of cure after treatment. More sensitive than cytology, primary screening by human papillomavirus testing could enable screening intervals to be extended. If these prevention strategies can be implemented in developing countries, many thousands of lives could be saved. Copyright © 2013 Elsevier Ltd. All rights reserved.
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              Brucellosis: an overview.

              M Corbel (1997)
              Brucellosis remains a major zoonosis worldwide. Although many countries have eradicated Brucella abortus from cattle, in some areas Brucella melitensis has emerged as a cause of infection in this species as well as in sheep and goats. Despite vaccination campaigns with the Rev 1 strain, B. melitensis remains the principal cause of human brucellosis. Brucella suis is also emerging as an agent of infection in cattle, thus extending its opportunities to infect humans. The recent isolation of distinctive strains of Brucella from marine mammals has extended its ecologic range. Molecular genetic studies have demonstrated phylogenetic affiliation to Agrobacterium, Phyllobacterium, Ochrobactrum, and Rhizobium. Polymerase chain reaction and gene probe development may provide more effective typing methods. Pathogenicity is related to production of lipopolysaccharides containing a poly N-formyl perosamine O chain, CuZn superoxide dismutase, erythrlose phosphate dehydrogenase, stress-induced proteins related to intracellular survival, and adenine and guanine monophosphate inhibitors of phagocyte functions. Protective immunity is conferred by antibody to lipopolysaccharide and T-cell-mediated macrophage activation triggered by protein antigens. Diagnosis still centers on isolation of the organism and serologic test results, especially enzyme immunoassay, which is replacing other methods. Polymerase chain reaction is also under evaluation. Therapy is based on tetracyclines with or without rifampicin, aminoglycosides, or quinolones. No satisfactory vaccines against human brucellosis are available, although attenuated purE mutants appear promising.
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                Author and article information

                Journal
                Hum Reprod Update
                Hum. Reprod. Update
                humupd
                humupd
                Human Reproduction Update
                Oxford University Press
                1355-4786
                1460-2369
                January 2016
                19 September 2015
                19 September 2015
                : 22
                : 1
                : 116-133
                Affiliations
                [1 ]Centre for Reproductive Health, University of Edinburgh , Edinburgh EH16 4TJ, UK
                [2 ]Moredun Research Institute , Pentlands Science Park, Bush Loan, Edinburgh EH26 0PZ, UK
                [3 ]Scottish HPV Reference Lab, Division of Lab Medicine, Royal Infirmary of Edinburgh , Edinburgh EH16 4SA, UK
                [4 ]The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh , Easter Bush, Midlothian EH25 9RG, UK
                [5 ]Centre for Inflammation Research, University of Edinburgh , Edinburgh EH16 4TJ, UK
                Author notes
                [* ]Correspondence address. E-mail: Andrew.Horne@ 123456ed.ac.uk
                Article
                dmv041
                10.1093/humupd/dmv041
                4664130
                26386469
                089d29c1-debf-430f-9741-59576da774e9
                © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

                History
                : 5 May 2015
                : 27 August 2015
                : 1 September 2015
                Funding
                Funded by: MRC Centre for Reproductive Health and Tommy's Charity
                Funded by: Biotechnology and Biological Sciences Research Council (BBSRC)/Zoetis Industrial Partnership
                Funded by: Scottish Government Rural and Environment Science and Analytical Services Division (RESAS)
                Categories
                Reviews
                Custom metadata
                January/February 2016

                Human biology
                miscarriage,infection,female tract,pregnancy
                Human biology
                miscarriage, infection, female tract, pregnancy

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