Himmelfarb Health Sciences Library, The George Washington University Health Sciences Research Commons Microbiology, Immunology, and Tropical Medicine Microbiology, Immunology, and Tropical Medicine Faculty Publications 3-2013 Break out: Urogenital schistosomiasis and Schistosoma haematobium infection in the post- genomic era Paul J. Brindley George Washington University Peter J. Hotez George Washington University Follow this and additional works at: http://hsrc.himmelfarb.gwu.edu/smhs_microbio_facpubs Part of the Medical Immunology Commons, Medical Microbiology Commons, Parasitic Diseases Commons, and the Parasitology Commons Recommended Citation Brindley, P.J. & Hotez, P.J. (2013). Break out: Urogenital schistosomiasis and Schistosoma haematobium infection in the post-genomic era. PLoS Neglected Tropical Diseases, 7(3), article number e1961. This Journal Article is brought to you for free and open access by the Microbiology, Immunology, and Tropical Medicine at Health Sciences Research Commons. It has been accepted for inclusion in Microbiology, Immunology, and Tropical Medicine Faculty Publications by an authorized administrator of Health Sciences Research Commons. For more information, please contact [email protected]. Editorial Break Out: Urogenital Schistosomiasis and Schistosoma haematobium Infection in the Post-Genomic Era Paul J. Brindley1*, Peter J. Hotez2,3* 1 Department of Microbiology, Immunology, and Tropical Medicine, George Washington University School of Medicine and Health Sciences, Washington DC, United States of America, 2 Departments of Pediatrics and Molecular Virology and Microbiology, National School of Tropical Medicine at Baylor College of Medicine, Houston, Texas, United States of America, 3 Sabin Vaccine Institute and Texas Children’s Hospital Center for Vaccine Development, Houston, Texas, United States of America The newly completed whole genome sequence of resulting female genital schistosomiasis and other chronic morbidities that use Schistosoma haematobium, the leading cause (FGS) is associated with contact bleeding, disability-adjusted life years (DALYs) as a of human schistosomiasis and an emerging co- discharge, pain on intercourse, and sec- metric suggests that chronic urogenital factor in Africa’s AIDS and cancer epidemics, ondary infections and diminished fertility; schistosomiasis may equal or even exceed together with rapidly advancing genetic manipula- it is also a source of shame and stigma malaria or other better-known conditions tion technologies, is providing new insights that [6,7]. FGS is not a rare condition—one in terms of its disease burden in Africa [4]. could lead to the development of a new generation estimate suggested that of the estimated 70 Despite its overwhelming public health of tools for eliminating this ancient scourge. million children currently infected with S. importance and its well-established links to Today, more than 90% of the roughly haematobium, approximately 19 million girls HIV/AIDS and cancer, S. haematobium has 200 million cases of schistosomiasis occur and women will eventually develop FGS been labeled ‘‘the neglected schistosome’’ in Africa [1,2], of which approximately in the coming decade [8]. However, these [10,11]. Indeed, as shown in Table 1, a two-thirds are caused by Schistosoma haema- numbers are likely conservative estimates, search of the literature named in PubMed tobium [3], the etiologic agent of urogenital such that FGS may represent one of the (the online database of the US National schistosomiasis. More recently, Charles most common gynecological conditions in Library of Medicine) supports this asser- King and his colleagues have suggested Africa. tion. Over the last five years, there have that the number of cases of S. haematobium In addition to the pathologies outlined been 644 papers listed in PubMed per may be much greater than previously above, the effects of chronic S. haematobium million cases of Asian schistosomiasis believed, even possibly double or triple infection in children have been linked to caused by Schistosoma japonicum and 25 that of earlier prevalence estimates [4]. If chronic inflammation and pain, as well as papers per million cases of S. mansoni confirmed, urogenital schistosomiasis may growth stunting and cognitive deficits infection, Africa’s other major schisto- represent the most common infection or among tens of millions of children [4]. some. In contrast, only three papers per even adverse health condition in sub- FGS has also been identified as a co-factor million cases of S. haematobium infection Saharan Africa. in Africa’s AIDS epidemic, especially in have appeared in PubMed over the last Urogenital schistosomiasis results when Zimbabwe and Tanzania, where it was five years. (The 342 publications over the adult female S. haematobium worm pairs linked to a 3–4 times increased risk in past five years investigating S. haematobium living in the veins draining key pelvic acquiring HIV infection [6–8]. S. haemato- and schistosomiasis haematobia represent organs, including the bladder, uterus, and bium eggs have now been further identified challenging research; and much effort cervix, release terminal-spine eggs that as a Group 1 carcinogen responsible for a went into studies on this organism during penetrate the tissues and are excreted in in unique squamous cell carcinoma, which is the several decades before that. Much of the urine to allow propagation of the parasite life cycle. However, many schis- widespread in S. haematobium–endemic this work was undertaken with humans as tosome eggs fail to exit the body, and areas [5,9]. S. haematobium also exerts the host, compounding the challenges for come to embolize within the capillary beds important host endocrine effects based in the research and encumbering progress. of pelvic end-organs, especially the tissues part on its ability to synthesize and release Although a review of this literature is of the bladder, ureters, and female and estradiol [9]. A full consideration of these beyond the aim of our editorial, studies male genital organs. Here they induce granulomas and ultimately small fibrotic Citation: Brindley PJ, Hotez PJ (2013) Break Out: Urogenital Schistosomiasis and Schistosoma haematobium nodules known as ‘‘sandy patches’’ [5]. Infection in the Post-Genomic Era. PLoS Negl Trop Dis 7(3): e1961. doi:10.1371/journal.pntd.0001961 Numerous granulomas and sandy patches Published March 28, 2013 cause bladder and ureteral inflammation Copyright: ß 2013 Hotez, Brindley. This is an open-access article distributed under the terms of the Creative associated with hematuria in more than Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, 50% of the cases [3], in addition to organ provided the original author and source are credited. deformities associated with ureteric ob- Funding: No specific funding was received for this work. struction, secondary urinary tract and Competing Interests: The authors have declared that no competing interests exist. renal infections, hydronephrosis, and ulti- * E-mail: [email protected] (PJB); [email protected] (PJH) mately renal failure in millions of people living in Africa [5]. Paul J. Brindley, PhD, is a Deputy Editor of PLOS Neglected Tropical Diseases. He is a professor in the Department of Microbiology, Immunology and Tropical Medicine, School of Medicine & Health Sciences, The George Up to 75% of girls and women with Washington University, Washington, DC. He is also the Scientific Director of the Research Center for Neglected chronic S. haematobium infection will also Diseases of Poverty at George Washington University. Peter J. Hotez, MD, PhD, is Co-Editor-in-Chief of PLOS experience deposition of eggs with granu- Neglected Tropical Diseases. He is President of the Sabin Vaccine Institute, Professor and Head of the Section of Pediatric Tropical Medicine in the Department of Pediatrics at Texas Children’s Hospital and Baylor College of lomas and sandy patches on their uterus, Medicine, and Dean of the National School of Tropical Medicine at Baylor College of Medicine in Houston, cervix, and lower genital tract [6,7]. The Texas, United States of America. PLOS Neglected Tropical Diseases | www.plosntds.org 1 March 2013 | Volume 7 | Issue 3 | e1961 Table 1. Number of citations in PubMed over the last five years, 2008–2012. Number of PubMed Approximate Number of Citations over the Last PubMed Citations per Parasite Species Human Cases Five Yearsb Millions of Human Cases References Schistosoma japonicum 1 million 644 644 Steinmann et al. 2006 [1] Schistosoma mansoni 54 milliona 1,371 25 Van der Werf et al. 2003 [3] Schistosoma haematobium 112 milliona 342 3 Van der Werf et al. 2003 [3] aSub-Saharan Africa only. bSearch conducted on July 14, 2012. doi:10.1371/journal.pntd.0001961.t001 such as those by Agnew, Cheever, and japonicum infections has stimulated at neocarcinogenesis of eggs in situ, and Doenhoff on rodent models of infection least two generations of molecular and molecules with immunomodulatory [12,13]; Capron and co-workers on vac- cellular immunologists to undertake functions. cines [14]; Feldmeier, Kjetland, Shiff, and groundbreaking studies on these two others on female genital schistosomiasis helminthiases and to unravel the com- It is particularly promising and of great and bladder cancer [7,9,15]; Brooker, plexities of schistosome-mediated im- importance that the development of Deelder, Hamburger, Mutapi, Sturrock, munopathogenesis [21–23]. Within the