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      Revisiting doxycycline in pregnancy and early childhood – time to rebuild its reputation?

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          ABSTRACT

          Introduction: Doxycycline is highly effective, inexpensive with a broad therapeutic spectrum and exceptional bioavailability. However these benefits have been overshadowed by its classification alongside the tetracyclines – class D drugs, contraindicated in pregnancy and in children under 8 years of age. Doxycycline-treatable diseases are emerging as leading causes of undifferentiated febrile illness in Southeast Asia. For example scrub typhus and murine typhus have an unusually severe impact on pregnancy outcomes, and current mortality rates for scrub typhus reach 12-13% in India and Thailand. The emerging evidence for these important doxycycline-treatable diseases prompted us to revisit doxycycline usage in pregnancy and childhood.

          Areas Covered: A systematic review of the available literature on doxycycline use in pregnant women and children revealed a safety profile of doxycycline that differed significantly from that of tetracycline; no correlation between the use of doxycycline and teratogenic effects during pregnancy or dental staining in children was found.

          Expert Opinion: The change of the US FDA pregnancy classification scheme to an evidence-based approach will enable adequate evaluation of doxycycline in common tropical illnesses and in vulnerable populations in clinical treatment trials, dosage-optimization pharmacokinetic studies and for the empirical treatment of undifferentiated febrile illnesses, especially in pregnant women and children.

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          Most cited references137

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          Rickettsioses as paradigms of new or emerging infectious diseases.

          Rickettsioses are caused by species of Rickettsia, a genus comprising organisms characterized by their strictly intracellular location and their association with arthropods. Rickettsia species are difficult to cultivate in vitro and exhibit strong serological cross-reactions with each other. These technical difficulties long prohibited a detailed study of the rickettsiae, and it is only following the recent introduction of novel laboratory methods that progress in this field has been possible. In this review, we discuss the impact that these practical innovations have had on the study of rickettsiae. Prior to 1986, only eight rickettsioses were clinically recognized; however, in the last 10 years, an additional six have been discovered. We describe the different steps that resulted in the description of each new rickettsiosis and discuss the influence of factors as diverse as physicians' curiosity and the adoption of molecular biology-based identification in helping to recognize these new infections. We also assess the pathogenic potential of rickettsial strains that to date have been associated only with arthropods, and we discuss diseases of unknown etiology that may be rickettsioses.
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            Mycoplasma genitalium: from Chrysalis to multicolored butterfly.

            The history, replication, genetics, characteristics (both biological and physical), and factors involved in the pathogenesis of Mycoplasma genitalium are presented. The latter factors include adhesion, the influence of hormones, motility, possible toxin production, and immunological responses. The preferred site of colonization, together with current detection procedures, mainly by PCR technology, is discussed. The relationships between M. genitalium and various diseases are highlighted. These diseases include acute and chronic nongonococcal urethritis, balanoposthitis, chronic prostatitis, and acute epididymitis in men and urethritis, bacterial vaginosis, vaginitis, cervicitis, pelvic inflammatory disease, and reproductive disease in women. A causative relationship, or otherwise strong association, between several of these diseases and M. genitalium is apparent, and the extent of this, on a subjective basis, is presented; also provided is a comparison between M. genitalium and two other genital tract-orientated mollicutes, namely, Mycoplasma hominis, the first mycoplasma of human origin to be discovered, and Ureaplasma species. Also discussed is the relationship between M. genitalium and infertility and also arthritis in both men and women, as is infection in homosexual and immunodeficient patients. Decreased immunity, as in HIV infections, may enhance mycoplasmal detection and increase disease severity. Finally, aspects of the antimicrobial susceptibility and resistance of M. genitalium, together with the treatment and possible prevention of mycoplasmal disease, are discussed.
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              Unresolved problems related to scrub typhus: a seriously neglected life-threatening disease.

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                Author and article information

                Journal
                Expert Opin Drug Saf
                Expert Opin Drug Saf
                IEDS
                ieds20
                Expert Opinion on Drug Safety
                Taylor & Francis
                1474-0338
                1744-764X
                3 March 2016
                25 January 2016
                : 15
                : 3
                : 367-382
                Affiliations
                [ a ]Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University , Mae Sot, Tak, Thailand
                [ b ]Mahidol-Oxford Tropical Medicine Research Unit (MORU), Faculty of Tropical Medicine, Mahidol University , Bangkok, Thailand
                [ c ]Centre for Tropical Medicine & Global Health, Nuffield Department of Clinical Medicine, University of Oxford , Oxford, UK
                Author notes
                CONTACT Daniel H. Paris parigi@ 123456tropmedres.ac Mahidol-Oxford Tropical Medicine Research Unit (MORU), 3rd Floor, 60th Anniversary Chalermprakiat Building, Faculty of Tropical Medicine, Mahidol University , 420/6 Rajvithee Rd, Bangkok 10400, Thailand
                Article
                1133584
                10.1517/14740338.2016.1133584
                4898140
                26680308
                b883d0e1-9f1e-40ec-8758-42f50822e5ef
                © 2016 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 20 October 2015
                : 15 December 2015
                Page count
                Figures: 1, Tables: 3, References: 140, Pages: 16
                Categories
                Review
                Reviews

                doxycycline,tetracycline,pregnancy,rickettsiosis,prenatal exposure,side effects,teratogenicity,major congenital anomalies,tooth discolouration,orientia tsutsugamushi,rickettsia typhi,scrub typhus,murine typhus,undifferentiated fever

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