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  • In conclusion this translational investigation

    2018-11-09

    In conclusion, this translational investigation identified gene candidates, including Marco, for host susceptibility to multiple phenotypes of RSV disease in mice that closely mimic human disease, and a polymorphism in human MARCO associated with increased risk of RSV disease severity in infants. Continued investigation of the genetic basis of differential susceptibility to RSV disease may lead to a panel of informative SNPs to identify children who are at risk for disease severity. In the absence of an RSV vaccine, these individuals could be treated prophylactically with an RSV monoclonal antibody to prevent infection and sequelae associated with severe disease such as childhood asthma.
    Funding Sources Research related to the manuscript was supported by the Intramural Research Program of the National Institutes of Health, NIEHS (Z01 ES 100557).
    Conflict of Interest Statement
    Author Contributions
    Acknowledgments
    Introduction Human yaws, a neglected tropical disease caused by T. pallidum subsp. pertenue (TPE), has been targeted for global eradication by 2020, after previous attempts in the 1950’s (Mitja et al., 2013) did not eradicate the disease (Asiedu et al., 2014). Factors involved in the natural history of yaws, including transmission by flies and a possible nonhuman reservoir (Knauf et al., 2013), may have contributed to yaws re-emergence. In humans, Treponema pallidum subsp. pallidum (TPA) causes syphilis, while TPE causes yaws (Lukehart, 2008; Giacani and Lukehart, 2014). We reported previously high levels of treponemal infection in nonhuman primates (NHPs) with strains closely related to the human yaws-causing strains (Knauf et al., 2013). This was shown on the basis of DNA polymorphisms that are known to distinguish among the subspecies of T. pallidum (Harper et al., 2012; Knauf et al., 2012) as well as on the basis of the mental health sequence of the Fribourg-Blanc strain (str. F-B) (Zobaníková et al., 2013), which was isolated from a baboon in Guinea in 1966 (Fribourg-Blanc and Mollaret, 1969). In addition, the subspecies of T. pallidum in humans (Sena et al., 2010) and those in NHPs (Knauf et al., 2015) are not distinguishable based on serology. The transmission of pathogenic treponemes by insects has been debated for over a century (Barnard, 1952a; Gudger, 1911; Gudger, 1910a; Gudger, 1910b; Barnard, 1952b; Lamborn, 1936), although there are no recent published studies. The observation that flies function as carriers of human pathogens such as Chlamydia trachomatis (causing blinding trachoma) under natural conditions has already been reported (Emerson et al., 2000; Emerson et al., 1999). In contrast, the role of necrophagous flies in the transmission of yaws and other treponematoses, despite the early notes and models at the beginning of the last century (Lamborn, 1936; Castellani, 1907; Kumm, 1935a; Kumm et al., 1935; Kumm and Turner, 1936; Satchell and Harrison, 1953), is not clear. Treponema species have not yet been reported to be present on necrophagous flies caught in a natural ecosystem and, most importantly, molecular evidence of the presence of the different subspecies has not been presented in any reported studies to date. In addition, a better understanding of different modes of transmission of T. pallidum is important for the development of sustainable control strategies. Vector transmission of the yaws bacterium for example, would underline the importance of additional hygiene measures and wound coverage when treating infected individuals. Moreover, if the simian yaws-like treponemes were demonstrated to be infectious to humans (Knauf et al., 2013), it could add an additional route of inter-species transmission. The West African simian isolate (str. F-B) is reported to have caused a sustained infection after experimental inoculation into humans (Smith et al., 1971). Based on previous reports, we hypothesized that flies function as a mechanical vector for the transmission of T. pallidum in areas of high prevalence of Treponema-induced skin ulceration in primates. To test this hypothesis, we performed a prospective cross-sectional study in areas that have populations of olive baboons (Papio anubis) with T. pallidum-associated genital ulcerations at Tarangire National Park (TNP; unpublished data) and Lake Manyara National Park (LMNP) (Knauf et al., 2012) in Tanzania.