A systematic review ofSchistosoma intercalatum: an obscure causative agent of human schistosomiasis

A systematic review of Schistosoma intercalatum: an obscure causative agent of human schistosomiasis | medRxiv /* */ /* */ <!-- <!-- /*! * yepnope1.5.4 * (c) WTFPL, GPLv2 */ (function(a,b,c){function d(a){return"[object Function]"==o.call(a)}function e(a){return"string"==typeof a}function f(){}function g(a){return!a||"loaded"==a||"complete"==a||"uninitialized"==a}function h(){var a=p.shift();q=1,a?a.t?m(function(){("c"==a.t?B.injectCss:B.injectJs)(a.s,0,a.a,a.x,a.e,1)},0):(a(),h()):q=0}function i(a,c,d,e,f,i,j){function k(b){if(!o&&g(l.readyState)&&(u.r=o=1,!q&&h(),l.onload=l.onreadystatechange=null,b)){"img"!=a&&m(function(){t.removeChild(l)},50);for(var d in y[c])y[c].hasOwnProperty(d)&&y[c][d].onload()}}var j=j||B.errorTimeout,l=b.createElement(a),o=0,r=0,u={t:d,s:c,e:f,a:i,x:j};1===y[c]&&(r=1,y[c]=[]),"object"==a?l.data=c:(l.src=c,l.type=a),l.width=l.height="0",l.onerror=l.onload=l.onreadystatechange=function(){k.call(this,r)},p.splice(e,0,u),"img"!=a&&(r||2===y[c]?(t.insertBefore(l,s?null:n),m(k,j)):y[c].push(l))}function j(a,b,c,d,f){return q=0,b=b||"j",e(a)?i("c"==b?v:u,a,b,this.i++,c,d,f):(p.splice(this.i++,0,a),1==p.length&&h()),this}function k(){var a=B;return a.loader={load:j,i:0},a}var l=b.documentElement,m=a.setTimeout,n=b.getElementsByTagName("script")[0],o={}.toString,p=[],q=0,r="MozAppearance"in l.style,s=r&&!!b.createRange().compareNode,t=s?l:n.parentNode,l=a.opera&&"[object Opera]"==o.call(a.opera),l=!!b.attachEvent&&!l,u=r?"object":l?"script":"img",v=l?"script":u,w=Array.isArray||function(a){return"[object Array]"==o.call(a)},x=[],y={},z={timeout:function(a,b){return b.length&&(a.timeout=b[0]),a}},A,B;B=function(a){function b(a){var a=a.split("!"),b=x.length,c=a.pop(),d=a.length,c={url:c,origUrl:c,prefixes:a},e,f,g;for(f=0;f<d;f++)g=a[f].split("="),(e=z[g.shift()])&&(c=e(c,g));for(f=0;f<b;f++)c=x[f](c);return c}function g(a,e,f,g,h){var i=b(a),j=i.autoCallback;i.url.split(".").pop().split("?").shift(),i.bypass||(e&&(e=d(e)?e:e[a]||e[g]||e[a.split("/").pop().split("?")[0]]),i.instead?i.instead(a,e,f,g,h):(y[i.url]?i.noexec=!0:y[i.url]=1,f.load(i.url,i.forceCSS||!i.forceJS&&"css"==i.url.split(".").pop().split("?").shift()?"c":c,i.noexec,i.attrs,i.timeout),(d(e)||d(j))&&f.load(function(){k(),e&&e(i.origUrl,h,g),j&&j(i.origUrl,h,g),y[i.url]=2})))}function h(a,b){function c(a,c){if(a){if(e(a))c||(j=function(){var a=[].slice.call(arguments);k.apply(this,a),l()}),g(a,j,b,0,h);else if(Object(a)===a)for(n in m=function(){var b=0,c;for(c in a)a.hasOwnProperty(c)&&b++;return b}(),a)a.hasOwnProperty(n)&&(!c&&!--m&&(d(j)?j=function(){var a=[].slice.call(arguments);k.apply(this,a),l()}:j[n]=function(a){return function(){var b=[].slice.call(arguments);a&&a.apply(this,b),l()}}(k[n])),g(a[n],j,b,n,h))}else!c&&l()}var h=!!a.test,i=a.load||a.both,j=a.callback||f,k=j,l=a.complete||f,m,n;c(h?a.yep:a.nope,!!i),i&&c(i)}var i,j,l=this.yepnope.loader;if(e(a))g(a,0,l,0);else if(w(a))for(i=0;i (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0];var j=d.createElement(s);var dl=l!='dataLayer'?'&l='+l:'';j.src='//www.googletagmanager.com/gtm.js?id='+i+dl;j.type='text/javascript';j.async=true;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-P4HH5NV'); Skip to main content Home About Submit ALERTS / RSS Search for this keyword Advanced Search A systematic review of Schistosoma intercalatum : an obscure causative agent of human schistosomiasis View ORCID Profile Oluwaremilekun Grace Ajakaye , Jean Pierre Kambala Mukendi , Eddy Laken Kakiese , Dieudonne Mumba Ngoyi , Masceline Jenipher Mutsaka-Makuvaza doi: https://doi.org/10.1101/2024.08.12.24311882 Oluwaremilekun Grace Ajakaye a Department of Animal and Environmental Biology, Adekunle Ajasin University , Akungba-Akoko, Ondo State, Nigeria Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Oluwaremilekun Grace Ajakaye For correspondence: oluwaremilekun.ajakaye{at}aaua.edu.ng Jean Pierre Kambala Mukendi b Department of Tropical Medicine, Infectious and Parasitic Diseases, Faculty of Medicine, University of Kinshasa , Kinshasa, Democratic Republic of the Congo c Department of Parasitology, Institut National de Recherche Biomédicale (INRB) , Kinshasa, Democratic Republic of the Congo Find this author on Google Scholar Find this author on PubMed Search for this author on this site Eddy Laken Kakiese c Department of Parasitology, Institut National de Recherche Biomédicale (INRB) , Kinshasa, Democratic Republic of the Congo Find this author on Google Scholar Find this author on PubMed Search for this author on this site Dieudonne Mumba Ngoyi b Department of Tropical Medicine, Infectious and Parasitic Diseases, Faculty of Medicine, University of Kinshasa , Kinshasa, Democratic Republic of the Congo c Department of Parasitology, Institut National de Recherche Biomédicale (INRB) , Kinshasa, Democratic Republic of the Congo Find this author on Google Scholar Find this author on PubMed Search for this author on this site Masceline Jenipher Mutsaka-Makuvaza d Department of Microbiology and Parasitology, School of Medicine and Pharmacy , University of Rwanda e National Institute of Health Research, Ministry of Health and Child Care , Zimbabwe Find this author on Google Scholar Find this author on PubMed Search for this author on this site Abstract Full Text Info/History Metrics Data/Code Preview PDF Abstract Background Human schistosomiasis caused by Schistosoma intercalatum is poorly understood compared to other species of public health importance, such as S. haematobium, S. mansoni , and S. japonicum . The restricted distribution of S. intercalatum in Africa, its perceived low virulence, and poor understanding of its pathological consequences are possible reasons for this neglect. However, schistosomiasis as a public health problem cannot be eradicated without adequate knowledge of existing species of schistosomes and the biological interactions between them, their hosts, and the environment. Current information on S. intercalatum is often confused with the previous S. intercalatum (Lower Guinea strain) which has now been described as S. guineensis n. sp. The S. intercalatum (Zaire strain) with known foci only in Democratic Republic of the Congo (DRC) is now recognized as the ‘true’ S. intercalatum species. Investigators not conversant with the present status of both species still get confused in understanding the literature hence this review. It is essential to discuss available knowledge on S. intercalatum and highlight gaps that are critical for deepening our understanding of the parasite in the DRC. Methods Thus, we systematically review existing available literature on S. intercalatum obtained from PubMed Central, Web of Science, Embase, and Scopus databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Relevant publications were screened and publications reporting S. intercalatum from other than the DRC were excluded. Eligible studies on the epidemiology and biology of S. intercalatum were reviewed. Results Based on 38 publications that met our inclusion criteria, we confirm that S. intercalatum is the most neglected among Schistosoma species responsible for human schistosomiasis. We discuss our synthesis of the available information in the context of the distribution, biology, pathology, and genetics of S. intercalatum . Also highlighted are outstanding questions on S. intercalatum population genomics, hybridization with other Schistosoma species, snail vector host, zoonotic epidemiology, and pathology. Conclusion The review calls for a rekindling of research interest in the parasite and the need to answer fundamental questions that can deepen our understanding of the parasite epidemiology, disease ecology, and environmental interactions to help in control strategies and elimination. Introduction Three parasitic worm species in the genus Schistosoma ( S. mansoni, S. japonicum , and S. haematobium ) are the widely recognized and studied causative agents of human schistosomiasis. Schistosoma japonicum and S. mansoni are responsible for intestinal schistosomiasis, while S. haematobium is responsible for urogenital schistosomiasis. Other species include S. guineensis, S. intercalatum, and S. mekongi, which have a lower global prevalence because of their localized distribution and, thus, are the least studied [ 1 , 2 ]. The adult stages of the parasites lodge in the host’s blood vessels within the intestinal or urogenital systems, where the mature female produces thousands of eggs, which are deposited in various tissues and organs, most notably the liver, bladder, small and large intestine, cervix, and vagina. Most disease pathology arises from inflammatory reactions and immune responses due to trapped eggs in the various organs. It can result in complications such as hepatosplenomegaly, periportal fibrosis, bladder cancer, and female genital schistosomiasis [ 1 , 2 ]. Although under-studied because of its localized distribution, and first identified in the Upper Congo by Chesterman, S. intercalatum is also of medical importance as responsible for rectal schistosomiasis. [ 3 ]. In 1934, Fisher [ 4 ] described the parasite as a new species of schistosome, and the features of the eggs essentially led to the name ’intercalatum ’ to underscore the intermediate profile when compared to eggs by S. haematobium and the bovine schistosome S. bovis [ 4 ]. Before the year 2003, two unique populations of S. intercalatum were recognized and marked by specific geographic locations, snail hosts, prepatent period in snail, egg morphometrics, isoenzyme patterns, Random Amplified Polymorphic DNA (RAPD), and Restriction Fragment Length Polymorphism (RFLP) [ 5 - 10 ]. Pages [ 11 ] supported by DNA sequencing data, grouped the S. intercalatum populations from the Lower Guinea forest region of Cameroon as a unique species described as S. guineensis n. sp. Other countries in the Lower Guinea forest region with reported foci for S. guineensis include Gabon, Equatorial Guinea, Nigeria, Benin Republic, and Sao Tome and Principe. Presently, S. intercalatum is known to have foci only in the Democratic Republic of the Congo (DRC) [ 12 , 13 ]. Although the distinct taxonomic status of S. intercalatum and S. guineensis was established in 2003, the large literature on S. intercalatum prior to 2003 has yet to be systematically reviewed and sorted according to species. Investigators not conversant with the present status of both species still get confused in understanding the literature. In this review, we focus only on literature pertaining to S. intercalatum species with known loci in the DRC. We discuss our synthesis of the available information in the context of the distribution, biology, pathology, and genetics of S. intercalatum . Methodology Eligibility Our primary objective was to compile peer-reviewed research publications, review articles, and case reports pertaining only to S. intercalatum species from the DRC. We aimed at synthesizing the information from all available publications from the 1900s till date. Our inclusion and exclusion criteria were based on the geographical source of the S. intercalatum reported in a publication. Literature reporting S. intercalatum originating from the DRC was included, while publications citing S. intercalatum originating from other African countries were considered as S. guineensis and thus excluded from our pool of literature for the review. Literature search strategy Three authors, OGA, JPKM, and ELK were responsible for the literature search and selection. Both JPKM and ELK are fluent French speakers and were therefore able to thoroughly appraise publications that were in the French language. A literature search of bibliographic databases Web of Science, EMBASE, SCOPUS, and PubMed Central was conducted between April 2022 and August 2023 for publications reported between the year 1900 to August 2023. To complement the database search, a manual search of publications was conducted by examining references from reviews and opinion articles on S. intercalatum or other Schistosoma species. Two search terms, “ Schistosoma intercalatum ” and “ intercalatum ” were used within field tags ‘Article Title,’ Abstract,’ and ‘Key Words’. Analysis of the retrieved literature complied with the reporting elements for systematic reviews guidelines prescribed in the PRISMA 2020 statement for reporting systematic reviews [ 14 ]. Results A total of 2,814 publications were retrieved from bibliographic databases, and after screening, 38 met the eligibility criteria and were used for full-text review ( Fig.1 ). Download figure Open in new tab Fig.1 PRISMA chart of literature selection process on Schistosoma intercalatum Discussion Schistosoma intercalatum in the DRC The history of S. intercalatum in the DRC dates to early 1900 in the regions around the former Belgian Congo (the present-day countries of DRC, the Republic of Congo, and parts of the Central African Republic). Several investigators reported terminal-spined S . haematobium -like eggs exclusively from stool samples in several foci in the Belgian Congo (see review in Fisher, [ 4 ]). Gillet and Wolfs [ 15 ] have also provided detailed historical accounts of the distribution and biology of three agents of schistosomiasis ( S. mansoni , S. haematobium , and S. intercalatum ) in the Belgian Congo. The last review of published research on schistosomiasis in the DRC confirmed the occurrence of one or more species of Schistosoma by microscopy ( S. mansoni , S. haematobium , and S. intercalatum ) in all but one of the provinces in the country [ 16 ]. The current prevalence rate of S. intercalatum is unknown. However, old reports based on microscopic analysis indicated it ranges between 1 and 10% [ 9 , 17 ], except for the study by Gillet and Wolfs [ 15 ] and Schwetz [ 18 ], which reported above 30%. Although there are no recent reports of the bovine schistosome S. bovis in the DRC, its occurrence has been documented previously [ 18 , 19 ]. In these studies, which used 781 cattle to determine the possible associations between different bovine trematode species in the Ituri region of the DRC, S. bovis adult worms were recovered from the mesenteric veins. Biology of S. intercalatum i. Lifecycle Schistosoma intercalatum lifecycle, larval and adult stages are similar to other known human Schistosoma species ( Fig. 2 ). Fisher [ 4 ] and Wright [ 5 ] have provided morphometric and behavioral information on the species from isolates originally derived from a patient in Kinshasa, which were experimentally passaged through infected mice or hamsters. Download figure Open in new tab Figure 2. The life-cycle of S. intercalatum and its hybrid. The cercariae of S. intercalatum and S. guineensis (formerly S. intercalatum , Lower Guinea strain) have been observed to concentrate near the surface of the water and readily attach to floating debris or the sides of a container in the laboratory, in contrast to S. mansoni cercariae, which typically swim to the surface of the water, rest briefly, and sink partially before swimming back [ 5 , 20 ]. ii. Snail host Crucial to the lifecycle of schistosomes are the appropriate intermediate snail hosts, and for S. intercalatum , Fisher [ 4 ] reported Physopsis africana (old nomenclature), now Bulinus africanus . However, the known difficulty in accurately morphologically identifying Bulinus species in Africa warrants the use of currently available molecular tools to aid species identification [ 8 , 21 - 23 ]. Wright et al. [ 5 ] were unsuccessful in infecting several Bulinus species ( B. africanus , B. globosus , B. ugandae , B. nasutus , B. forskalii , and B. camerunensis ) that had been collected from various countries in Africa and bred in the lab with S. intercalatum . Only B. globosus from South Africa, Ghana, Zimbabwe, Sudan, and B. wrighti from Saudi Arabia were successfully infected. However, Wright et al. [ 5 ] observed a lengthier prepatent period compared with other species of Schistosoma investigated in the study. Frandsen [ 6 , 24 ], however, demonstrated successful experimental S. intercalatum infections of B. globosus from Malawi, Togo, Rhodesia (Zimbabwe), and DRC. Interestingly, B. africanus from Kenya and Tanzania were susceptible to S. intercalatum , while the albino strain of B. globosus from Zimbabwe was the most compatible compared to other snail species successfully infected. De Clercq [ 17 ] also confirmed B. globosus as natural hosts for S. intercalatum in the DRC. However, Tchuem Tchuenté et al. [ 9 ] were unsuccessful in finding naturally infected snails for S. intercalatum in the DRC but reported similar experimental results reported by Wright et al. [ 5 ]. The snail infection trials demonstrated incompatibility between S. intercalatum and B. forskalii , B. truncatus/B. tropicus complex, and B. africanus group, except for B. globosus from Zambia and B. wrighti snails. Although Frandsen [ 6 , 24 ] has done extensive snail host specificity experiments for S. intercalatum , they were by no means exhaustive of the diversity of Bulinus species in Africa [ 8 ]. Also, the susceptibility and compatibility of other non- Bulinus species to S. intercalatum are yet unknown. How snail hosts genetic diversity impacts S. intercalatum presents an intriguing line of research, and in the scenario of hybridization between S. intercalatum and other Schistosoma species, it would be essential to determine if hybrid S. intercalatum recruits new snail hosts. Questions on the genetic basis of Bulinus - S. intercalatum interaction is unanswered. On the possibility of control strategies targeting snail hosts, there is a need to identify genes that convey natural resistance to S. intercalatum in Bulinus species, which may facilitate ways of disrupting the parasite’s life cycle and reducing transmission to humans. iii. Reservoir hosts Unlike the two main agents of intestinal schistosomiasis ( S. mansoni and S. japonicum ) with a broad spectrum of reservoir hosts, no known natural reservoir hosts for S. intercalatum in the DRC have been identified. Monkeys, Congo clawless otters ( Aonyx congica ), sheep, and goats examined for S. intercalatum by Fisher [ 4 ] were uninfected. However, Fisher [ 4 ] successfully infected a male sheep with cercariae of S. intercalatum . Schwetz [ 18 ] was also able to infect both sheep and goats with S. intercalatum using the same route of infection as by Fisher [ 4 ], although no one else has ever tried this route to confirm these findings. The role of animal reservoir hosts in S. intercalatum transmission remains unexplored. Fisher [ 4 ] and Schwetz [ 18 ] examined a few mammalian species without recording any natural host for S. intercalatum. Several species of rodents across Africa are known to serve as natural reservoir hosts of several species of Schistosoma and hybrid S. haematobium x S. bovis [ 25 , 26 ]. The rodent species frequenting water bodies in schistosomiasis endemic communities in the DRC will be interesting for investigation. There is now a wide range of molecular approaches for detecting pathogens that do not require invasive sampling. Also, environmental DNA techniques provide an opportunity for detecting nucleic acid traces in various environmental samples [ 27 - 29 ]. Pathology of S. intercalatum There is generally a dearth of information on the clinical aspects of S. intercalatum due to limited studies on the parasite. There is a need for an adequate understanding of the pathological impacts of the parasite to inform necessary control and elimination strategies. Fisher [ 4 ] and Schwetz [ 18 ] have highlighted several S. intercalatum clinical signs similar to other intestinal human schistosomiasis caused by S. mansoni , S . guineensis , and S. japonicum . Wolfe [ 30 ] provided a case report of an American family returning to the USA from Kisangani, Eastern DRC who were infected with S. intercalatum after parasitological examination of stool. The common symptoms that have been reported include abdominal pain, blood in stool, dysentery, and a few cases of palpable, enlarged livers. None of the reported cases showed any marked degree of anemia. Molecular epidemiology of S. intercalatum Before the separation of the Lower Guinea strain of S. intercalatum (now S. guineensis ) from the DRC S. intercalatum species, genotyping studies of both species were performed using isoenzyme patterns, Random Amplified Polymorphic DNA (RAPD) and Restriction Fragment Length Polymorphism (RFLP) [ 7 - 9 ]. DNA-sequence data based on three mitochondrial genes, (cytochrome oxidase subunit 1 (cox1), NADH dehydrogenase subunit 6 (nad6) and small ribosomal RNA (rrnS)) was pivotal evidence for the eventual distinctions between the two species and the subsequent description of S. guineensis [ 10 - 12 ]. Presently the available DNA sequence data on S. intercalatum archived on the NCBI nucleotide database is problematic because some of the sequences labeled as S. intercalatum are that of S. guineensis [ 11 - 13 ] ( Table 1 ). Unfortunately, most nucleotide sequences deposited at the NCBI are rarely revised or corrected after their initial submission. Apart from sequence alignments consistent with the phylogram reported in [ 11 , [ 12 ], and [ 13 ], users can quickly ascertain the NCBI sequence data on S. intercalatum by checking the country of origin of the isolate ( S. intercalatum will expectedly be from DRC). Webster et al. [ 13 ] have also provided information for the correct taxonomic names for sequences on the NCBI nucleotide database labeled as S. intercalatum (now S. guineensis ) and those from DRC representing S. intercalatum . View this table: View inline View popup Table 1. Correct names for nucleotide sequences labeled as Schistosoma intercalatum on NCBI Table 1 . Correct names for nucleotide sequences labeled as Schistosoma intercalatum on NCBI Outstanding questions on S. intercalatum Although schistosomiasis is considered a neglected tropical disease, S. intercalatum appears to be the most neglected among the species that cause human schistosomiasis. It is probably due to the difficulty in accessing new specimens from DRC after decades of protracted conflicts and insecurity in the country. The genetic basis for the restricted distribution of S. intercalatum is still unknown. However, the availability of modern DNA sequencing technologies, including Next Generation Sequencing (NGS), provides an opportunity for robust genomic investigations on S. intercalatum . Some outstanding questions still in need of answers include: Genetic diversity and population genetics / genomics : Compared to other Schistosoma species of medical importance, there is no information on the genetic diversity or population genetics of S. intercalatum . Given the large landmass area of the DRC with its diverse ecological zones and abundant wildlife, it would be interesting to unravel the evolutionary dynamics of the parasite over time. Hybridization : Interspecific hybridization has been demonstrated to occur in the laboratory within the S. haematobium species complex, which is comprised of eight sister species including S. intercalatum , S. guineensis , S. bovis , S. mattheei , S. margrebowei , S. leiperi , S. curassoni, and S. kisumuensis) [ 37 , 38 ]. Increasingly, hybrids are being recovered from field sites, but the true extent to which this is occurring in nature remains enigmatic. This is largely because no systematic genotyping strategy exists, and only limited gene markers or genome-scale datasets have been derived from Schistosoma samples collected from natural infections. To date, interspecific hybrids within the S. haematobium group species have been described especially between S. haematobium x S. bovis (reviewed in [ 39 ]), S. haematobium x S. guineensis [ 38 ], S. haematobium x S. mattheei [ 39 ] and S. bovis x S. curassoni [ 40 ]. DNA sequence data has thus far not identified any field isolates that exist as S. intercalatum hybrids with other Schistosoma species, although, based on isoenzyme analysis, Tchuem Tchuenté et al. [ 9 ] reported that natural hybridization is occurring between S. haematobium and S. intercalatum in the DRC. The reference genome for S. intercalatum, sequenced as part of a consortia project [ 41 ] is freely available on the NCBI Short Read Archives (see [ 40 ] for details) and appears to be devoid of mixed ancestry. However, previous S. intercalatum hybridization experiments with S. guineensis or S. mansoni have established that S. intercalatum is mating competent under laboratory conditions with its sister species, S. guineensis [ 42 - 44 ]. Through a suite of genome analysis tools, it is now possible to analyse the direction of introgression within inter species hybrids, to identify introgressed genes, and to establish whether the hybrids could alter virulence phenotypes [ 37 , 45 ]. Epidemiology and pathology : Tchuem Tchuenté [ 9 ], to our knowledge, is the last peer-reviewed publication on the epidemiology of S. intercalatum from the DRC. There is a need for a nationwide epidemiological survey to determine the current prevalence of S. intercalatum or its hybrid in the DRC and neighbouring countries and detailed documentation of clinical signs of the disease. Importantly, molecular studies of samples from such nationwide surveys will provide information to understand if S. intercalatum has been entirely replaced by S. haematobium as was reported for S. guineensis replacement by S. haematobium in [ 46 - 48 ]. Conclusion Arguably, the 1990s intense security challenges in the DRC affected the study of S. intercalatum . Now that the security in the DRC has improved, there is a need for renewed interest in studying S. intercalatum . While lessons learned from current research in Africa on the two major African human schistosome species, S. mansoni and S. haematobium , can be applied in other endemic regions, there is no such scenario for S. intercalatum . It is of epidemiological importance to know the degree to which S. intercalatum is cross-hybridizing vs. inbreeding and whether this is impacting the incidence and severity of rectal schistosomiasis in the country. In light of the World Health Organization’s roadmap for the elimination of human schistosomiasis, an understanding of the molecular epidemiology of all causative agents and the complex interactions between them, their various host species, and the disease ecology are all vital. Declarations Ethics approval and consent to participate Not Applicable Consent for publication Not Applicable Availability of data and materials All data generated or analysed during this study are included in this published article. Competing Interest The authors declare no conflict of interest. Funding This research received no external funding. Author Contributions OGA, ELK and JPKM did the literature searches; OGA and JPKM wrote the manuscript. JPKM and MJM updated the text; ELK and DMN reviewed the manuscript; and OGA and JPKM organized and edited the final manuscript. Data Availability All data produced in the present work are contained in the manuscript Acknowledgements We would like to thank Elisha Enabulele for generating the outstanding figure, and Michael Grigg for critical reading of the manuscript. References 1. ↵ Colley DG , Bustinduy AL , Secor WE , King CH . Human schistosomiasis . Lancet . 2014 Jun 28; 383 ( 9936 ): 2253-64 . doi: 10.1016/S0140-6736(13)61949-2 . OpenUrl CrossRef 2. ↵ McManus DP , Dunne DW , Sacko M , Utzinger J , Vennervald BJ , Zhou XN . Schistosomiasis . Nat Rev Dis Primers . 2018 Aug 9; 4 ( 1 ): 13 . doi: 10.1038/s41572-018-0013-8 . OpenUrl CrossRef PubMed 3. ↵ Chesterman CC . Note sur la bilharziose dans la region de Stanleyvirle . Ann. Soc. Belg. Med. Trop ., 1923 , 3 , 73 – 75 . OpenUrl 4. ↵ Fisher AC . A study of the schistosomiasis of the Stanleyville district of the Belgian congo . Transactions of Trans. R. Soc. Trop. Med. Hyg. T ROY SOC TROP MED H , 1934 ; 28 ( 3 ), 277 – 306 , doi: 10.1016/S0035-9203(34)90066-3 . OpenUrl CrossRef 5. ↵ Wright CA , Southgate VR , Knowles RJ . What is Schistosoma intercalatum Fisher, 1934? Trans R Soc Trop Med Hyg . 1972 ; 66 ( 1 ): 28-64 . doi: 10.1016/0035-9203(72)90052-1 . OpenUrl CrossRef 6. ↵ Frandsen F. Hybridization between different strains of Schistosoma intercalatum Fisher, 1934 from Cameroun and Zaïre. J Helminthol . 1978 Mar; 52 ( 1 ): 11-22 . doi: 10.1017/s0022149x0000506x . OpenUrl CrossRef 7. ↵ Wright CA , Southgate VR , Ross GC . Enzymes in Schistosoma intercalatum and the relative status of the Lower Guinea and Zaire strains of the parasite . Int J Parasitol . 1979 Dec ; 9 ( 6 ): 523 – 8 . doi: 10.1016/0020-7519(79)90007-9 . OpenUrl CrossRef PubMed 8. ↵ Brown DS , Sarfati C , Southgate VR , Ross GC , Knowles RJ . Observations on Schistosoma intercalatum in south-east Gabon . Z Parasitenkd . 1984 ; 70 ( 2 ): 243 – 53 . doi: 10.1007/BF00942227 . OpenUrl CrossRef PubMed 9. ↵ Tchuem Tchuenté LA , Southgate VR , Vercruysse J , Kaukas A , Kane R , Mulumba MP , Pagès JR , Jourdane J . Epidemiological and genetic observations on human schistosomiasis in Kinshasa, Zaire . Trans R Soc Trop Med Hyg . 1997 May-Jun ; 91 ( 3 ): 263-9 . doi: 10.1016/s0035-9203(97)90068-7 . OpenUrl CrossRef 10. ↵ Pagès JR , Durand P , Southgate VR , Tchuem Tchuenté LA , Jourdane J . Molecular arguments for splitting of Schistosoma intercalatum, into two distinct species . Parasitol Res . 2001 Jan ; 87 ( 1 ): 57 – 62 . doi: 10.1007/s004360000301 . OpenUrl CrossRef PubMed 11. ↵ Pages J.R. , Jourdane J. , Southgate V.R. & Tchuem Tchuenté L.A . 2003 . Reconnaissance de deux espèces jumelles au sein du taxon Schistosoma intercalatum Fisher, 1934, agent de la schistosomose humaine rectale en Afrique. Description de Schistosoma guineensis n. sp. In: Tax, Ecol Evol Metz Parasit. Tome II. Combes C. & Jourdane J. (eds) . Presses Universitaires de Perpignan , 139 – 146 . 12. ↵ Kane RA , Southgate VR , Rollinson D , Littlewood DT , Lockyer AE , Pagès JR , Tchuem Tchuentè LA , Jourdane J . A phylogeny based on three mitochondrial genes supports the division of Schistosoma intercalatum into two separate species . Parasitology . 2003 Aug ; 127 (Pt 2 ): 131 – 7 . doi: 10.1017/s0031182003003421 . OpenUrl CrossRef 13. ↵ Webster BL , Southgate VR , Littlewood DT . A revision of the interrelationships of Schistosoma including the recently described Schistosoma guineensis . Int J Parasitol . 2006 Jul ; 36 ( 8 ): 947 – 55 . doi: 10.1016/j.ijpara.2006.03.005 . OpenUrl CrossRef PubMed Web of Science 14. ↵ Page MJ , McKenzie JE , Bossuyt PM , Boutron I , Hoffmann TC , Mulrow CD , Shamseer L , Tetzlaff JM , Akl EA , Brennan SE , Chou R , Glanville J , Grimshaw JM , Hróbjartsson A , Lalu MM , Li T , Loder EW , Mayo-Wilson E , McDonald S , McGuinness LA , Stewart LA , Thomas J , Tricco AC , Welch VA , Whiting P , Moher D . The PRISMA 2020 statement: an updated guideline for reporting systematic reviews . BMJ . 2021 Mar 29; 372 :n71. doi: 10.1136/bmj.n71 . OpenUrl FREE Full Text 15. ↵ Gillet J , Wolfs J . Les bilharzioses humaines au Congo Belge et au Ruanda-Urundi [Bilharziosis in the Belgian Congo and in Ruanda-Urundi] . Bull World Health Organ . 1954 ; 10 ( 3 ): 315 – 419 . OpenUrl PubMed 16. ↵ Madinga J , Linsuke S , Mpabanzi L , Meurs L , Kanobana K , Speybroeck N , Lutumba P , Polman K . Schistosomiasis in the Democratic Republic of Congo: a literature review . Parasit Vectors . 2015 Nov 19; 8 : 601 . doi: 10.1186/s13071-015-1206-6 . OpenUrl CrossRef PubMed 17. ↵ De Clercq D . La situation malacologique à Kinshasa et description d’un foyer autochtone de schistosomiase à Schistosoma intercalatum [The malacological situation in Kinshasa and description of an aotochthonous focus of schistosomiasis due to Schistosoma intercalatum] . Ann Soc Belg Med Trop . 1987 Dec ; 67 ( 4 ): 345 – 52 . OpenUrl PubMed 18. ↵ Schwetz J . Some new comparative investigations on three Physopsis borne schistosomes: Schistosoma haematobium , Schistosoma bovis and Schistosoma intercalatum . Am. J. Trop. Med. Hyg ., 1956 , 5 , 1071 – 1085 . OpenUrl Abstract / FREE Full Text 19. ↵ Chartier C , Bushu M , Anican U . Les dominantes du parasitisme helminthique chez les bovins en Ituri (Haut-Zaïre) . II. Les associations parasitaires [Characteristics of helminthic parasitism in cattle in Ituri (Haut-Zaire). II. Parasitic associations]. Rev Elev Med Vet Pays Trop . 1990 ; 43 ( 4 ): 491 – 7 . OpenUrl 20. ↵ Lewis F . https://afbr-bri.org/schistosomiasis/standard-operating-procedures/behavior-of-schistosoma-mansoni-cercariae/ Accessed 15th of March, 2024 21. ↵ Kane RA , Stothard JR , Emery AM , Rollinson D . Molecular characterization of freshwater snails in the genus Bulinus: a role for barcodes? Parasit Vectors . 2008 Jun 10; 1 ( 1 ): 15 . doi: 10.1186/1756-3305-1-15 . OpenUrl CrossRef PubMed 22. Zhang SM , Bu L , Lu L , Babbitt C , Adema CM , Loker ES . Comparative mitogenomics of freshwater snails of the genus Bulinus, obligatory vectors of Schistosoma haematobium, causative agent of human urogenital schistosomiasis . Sci Rep . 2022 Mar 30; 12 ( 1 ): 5357 . doi: 10.1038/s41598-022-09305-7 . OpenUrl CrossRef 23. ↵ Babbitt CR , Laidemitt MR , Mutuku MW , Oraro PO , Brant SV , Mkoji GM , Loker ES . Bulinus snails in the Lake Victoria Basin in Kenya: Systematics and their role as hosts for schistosomes . PLoS Negl Trop Dis . 2023 Feb 10; 17 ( 2 ): e0010752 . doi: 10.1371/journal.pntd.0010752 . OpenUrl CrossRef 24. ↵ Frandsen F . Further studies on the compatibility between S. intercalatum from cameroun and zaïre and species of bulinus . Z Parasitenkd . 1979 Feb 28; 58 ( 2 ): 161 – 7 . doi: 10.1007/BF01951340 . OpenUrl CrossRef PubMed 25. ↵ Standley CJ , Dobson AP , Stothard JR . Out of animals and back again: schistosomiasis as a zoonosis in Africa. In: Rokni MB, ed. Schistosomiasis. InTech 2012 : 209–230 . ISBN: 978-953-307-852-6. 26. ↵ Catalano S , Sène M , Diouf ND , Fall CB , Borlase A , Léger E , Bâ K , Webster JP . Rodents as Natural Hosts of Zoonotic Schistosoma Species and Hybrids: An Epidemiological and Evolutionary Perspective From West Africa . J Infect Dis . 2018 Jul 2; 218 ( 3 ): 429 – 433 . doi: 10.1093/infdis/jiy029 . OpenUrl CrossRef PubMed 27. ↵ Farrell JA , Whitmore L , Duffy DJ . The Promise and Pitfalls of Environmental DNA and RNA Approaches for the Monitoring of Human and Animal Pathogens from Aquatic Sources . Bioscience . 2021 Apr 21:biab027. doi: 10.1093/biosci/biab027 . OpenUrl CrossRef 28. Schilling AK , Mazzamuto MV , Romeo C . A Review of Non-Invasive Sampling in Wildlife Disease and Health Research: What’s New? Animals (Basel ). 2022 Jul 2; 12 ( 13 ): 1719 . doi: 10.3390/ani12131719 . OpenUrl CrossRef 29. ↵ Bass D , Christison KW , Stentiford GD , Cook LSJ , Hartikainen H . Environmental DNA/RNA for pathogen and parasite detection, surveillance, and ecology . Trends Parasitol . 2023 Apr ; 39 ( 4 ): 285 – 304 . doi: 10.1016/j.pt.2022.12.010 . OpenUrl CrossRef 30. ↵ Wolfe MS . Schistosoma intercalatum infection in an American family . Am J Trop Med Hyg . 1974 Jan ; 23 ( 1 ): 45 – 50 . doi: 10.4269/ajtmh.1974.23.45 . OpenUrl Abstract / FREE Full Text 31. Lockyer AE , Olson PD , Ostergaard P , Rollinson D , Johnston DA , Attwood SW , Southgate VR , Horak P , Snyder SD , Le TH , Agatsuma T , McManus DP , Carmichael AC , Naem S , Littlewood DT . The phylogeny of the Schistosomatidae based on three genes with emphasis on the interrelationships of Schistosoma Weinland, 1858. Parasitology . 2003 Mar; 126 ( Pt 3 ): 203-24 . doi: 10.1017/s0031182002002792 . OpenUrl CrossRef 32. Sealey KL , Kirk RS , Walker AJ , Rollinson D , Lawton SP . Adaptive radiation within the vaccine target tetraspanin-23 across nine Schistosoma species from Africa . Int J Parasitol . 2013 Jan ; 43 ( 1 ): 95 – 103 . doi: 10.1016/j.ijpara.2012.11.007 . OpenUrl CrossRef PubMed 33. Bowles J , Blair D , McManus DP . A molecular phylogeny of the human schistosomes . Mol Phylogenet Evol . 1995 Jun ; 4 ( 2 ): 103 – 9 . doi: 10.1006/mpev.1995.1011 . OpenUrl CrossRef PubMed 34. Abbasi I , King CH , Sturrock RF , Kariuki C , Muchiri E , Hamburger J . Differentiation of Schistosoma haematobium from related schistosomes by PCR amplifying an inter-repeat sequence . Am J Trop Med Hyg . 2007 May ; 76 ( 5 ): 950 – 5 . OpenUrl Abstract / FREE Full Text 35. Barker SC , Blair D . Molecular phylogeny of Schistosoma species supports traditional groupings within the genus . J Parasitol . 1996 Apr ; 82 ( 2 ): 292 – 8 . OpenUrl CrossRef PubMed 36. Michot B , Despres L , Bonhomme F , Bachellerie JP . Conserved secondary structures in the ITS2 of trematode pre-rRNA . FEBS Lett . 1993 Feb 1; 316 ( 3 ): 247 – 52 . doi: 10.1016/0014-5793(93)81301-f . OpenUrl CrossRef PubMed Web of Science 37. ↵ Leger E , Webster JP . Hybridizations within the Genus Schistosoma: implications for evolution, epidemiology and control . Parasitology . 2017 Jan ; 144 ( 1 ): 65 – 80 . doi: 10.1017/S0031182016001190 . Epub 2016 Aug 30 pmid: . PMID: 27572906 . OpenUrl CrossRef PubMed 38. ↵ Landeryou T , Rabone M , Allan F , Maddren R , Rollinson D , Webster BL , Tchuem-Tchuenté LA , Anderson RM , Emery AM . Genome-wide insights into adaptive hybridisation across the Schistosoma haematobium group in West and Central Africa . PLoS Negl Trop Dis . 2022 Jan 31; 16 ( 1 ): e0010088 . doi: 10.1371/journal.pntd.0010088 . OpenUrl CrossRef PubMed 39. ↵ Rey O , Webster BL , Huyse T , Rollinson D , Van den Broeck F , Kincaid-Smith J , Onyekwere A , Boissier J . Population genetics of African Schistosoma species . Infect Genet Evol . 2021 Apr ; 89 : 104727 . doi: 10.1016/j.meegid.2021.104727 . OpenUrl CrossRef 40. ↵ Berger DJ , Léger E , Sankaranarayanan G , Sène M , Diouf ND , Rabone M , Emery A , Allan F , Cotton JA , Berriman M , Webster JP . Genomic evidence of contemporary hybridization between Schistosoma species . PLoS Pathog . 2022 Aug 8; 18 ( 8 ): e1010706 . doi: 10.1371/journal.ppat.1010706 . OpenUrl CrossRef PubMed 41. ↵ IHGCCG-International Helminth Genomes Consortium . Comparative genomics of the major parasitic worms. Nat Genet . 2019 Jan; 51 ( 1 ): 163-174 . doi: 10.1038/s41588-018-0262-1 . Epub 2018 Nov 5 . OpenUrl CrossRef 42. ↵ Bjørneboe A , Frandsen F . A comparison of the characteristics of two strains of Schistosoma intercalatum Fisher , 1934 in mice. J Helminthol. 1979 Sep;53(3):195-203. doi: 10.1017/s0022149x00005976 . OpenUrl CrossRef 43. Pagès JR , Southgate VR , Tchuem Tchuenté LA , Jourdane J . Experimental evidence of hybrid breakdown between the two geographical strains of Schistosoma intercalatum . Parasitology . 2002 Feb ; 124 (Pt 2 ): 169 – 75 . doi: 10.1017/s0031182001001068 . OpenUrl CrossRef 44. ↵ Cosgrove CL , Southgate VR . Interactions between Schistosoma intercalatum (Zaire strain) and S. mansoni . J Helminthol . 2003 Sep ; 77 ( 3 ): 209 – 18 . doi: 10.1079/JOH2002165 . OpenUrl CrossRef PubMed 45. ↵ Moran BM , Payne C , Langdon Q , Powell DL , Brandvain Y , Schumer M . The genomic consequences of hybridization . Elife . 2021 Aug 4; 10 : e69016 . doi: 10.7554/eLife.69016 . OpenUrl CrossRef 46. ↵ Tchuem Tchuenté LA , Southgate VR , Njiokou F , Njiné T , Kouemeni LE , Jourdane J . The evolution of schistosomiasis at Loum , Cameroon: replacement of Schistosoma intercalatum by S. haematobium through introgressive hybridization. Trans R Soc Trop Med Hyg . 1997b Nov-Dec ; 91 ( 6 ): 664-5 . doi: 10.1016/s0035-9203(97)90513-7 . OpenUrl CrossRef 47. Webster BL , Tchuem Tchuenté LA , Jourdane J , Southgate VR . The interaction of Schistosoma haematobium and S. guineensis in Cameroon . J Helminthol . 2005 Sep ; 79 ( 3 ): 193 – 7 . doi: 10.1079/joh2005306 . OpenUrl CrossRef PubMed 48. ↵ Kabore A , Ibikounle M , Tougoue JJ , Mupoyi S , Ndombe M , Shannon S , Ottesen EA , Mukunda F , Awaca N . Initiating NTD programs targeting schistosomiasis and soil-transmitted helminthiasis in two provinces of the Democratic Republic of the Congo. Establishment of baseline prevalence for mass drug administration . Acta Trop . 2017 Feb ; 166 : 177 – 185 . doi: 10.1016/j.actatropica.2016.11.023 . OpenUrl CrossRef PubMed View the discussion thread. Back to top Previous Next Posted August 13, 2024. Download PDF Data/Code Email Thank you for your interest in spreading the word about medRxiv. NOTE: Your email address is requested solely to identify you as the sender of this article. Your Email * Your Name * Send To * Enter multiple addresses on separate lines or separate them with commas. You are going to email the following A systematic review of Schistosoma intercalatum: an obscure causative agent of human schistosomiasis Message Subject (Your Name) has forwarded a page to you from medRxiv Message Body (Your Name) thought you would like to see this page from the medRxiv website. Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions. Share A systematic review of Schistosoma intercalatum : an obscure causative agent of human schistosomiasis Oluwaremilekun Grace Ajakaye , Jean Pierre Kambala Mukendi , Eddy Laken Kakiese , Dieudonne Mumba Ngoyi , Masceline Jenipher Mutsaka-Makuvaza medRxiv 2024.08.12.24311882; doi: https://doi.org/10.1101/2024.08.12.24311882 Share This Article: Copy Citation Tools A systematic review of Schistosoma intercalatum : an obscure causative agent of human schistosomiasis Oluwaremilekun Grace Ajakaye , Jean Pierre Kambala Mukendi , Eddy Laken Kakiese , Dieudonne Mumba Ngoyi , Masceline Jenipher Mutsaka-Makuvaza medRxiv 2024.08.12.24311882; doi: https://doi.org/10.1101/2024.08.12.24311882 Citation Manager Formats BibTeX Bookends EasyBib EndNote (tagged) EndNote 8 (xml) Medlars Mendeley Papers RefWorks Tagged Ref Manager RIS Zotero Tweet Widget Facebook Like Google Plus One Subject Area Infectious Diseases (except HIV/AIDS) Subject Areas All Articles Addiction Medicine (573) Allergy and Immunology (865) Anesthesia (302) Cardiovascular Medicine (4453) Dentistry and Oral Medicine (444) Dermatology (383) Emergency Medicine (609) Endocrinology (including Diabetes Mellitus and Metabolic Disease) (1515) Epidemiology (15242) Forensic Medicine (30) Gastroenterology (1131) Genetic and Genomic Medicine (6615) Geriatric Medicine (669) Health Economics (1001) Health Informatics (4552) Health Policy (1372) Health Systems and Quality Improvement (1614) Hematology (543) HIV/AIDS (1270) Infectious Diseases (except HIV/AIDS) (15929) Intensive Care and Critical Care Medicine (1106) Medical Education (624) Medical Ethics (147) Nephrology (670) Neurology (6625) Nursing (346) Nutrition (999) Obstetrics and Gynecology (1148) Occupational and Environmental Health (957) Oncology (3344) Ophthalmology (979) Orthopedics (369) Otolaryngology (421) Pain Medicine (436) Palliative Medicine (130) Pathology (665) Pediatrics (1696) Pharmacology and Therapeutics (693) Primary Care Research (714) Psychiatry and Clinical Psychology (5461) Public and Global Health (9252) Radiology and Imaging (2207) Rehabilitation Medicine and Physical Therapy (1371) Respiratory Medicine (1197) Rheumatology (597) Sexual and Reproductive Health (715) Sports Medicine (530) Surgery (714) Toxicology (99) Transplantation (289) Urology (265) (function(){function c(){var b=a.contentDocument||a.contentWindow.document;if(b){var d=b.createElement('script');d.innerHTML="window.__CF$cv$params={r:'a02f1c532ce1300f',t:'MTc3OTk5MDcyMA=='};var a=document.createElement('script');a.src='/cdn-cgi/challenge-platform/scripts/jsd/main.js';document.getElementsByTagName('head')[0].appendChild(a);";b.getElementsByTagName('head')[0].appendChild(d)}}if(document.body){var a=document.createElement('iframe');a.height=1;a.width=1;a.style.position='absolute';a.style.top=0;a.style.left=0;a.style.border='none';a.style.visibility='hidden';document.body.appendChild(a);if('loading'!==document.readyState)c();else if(window.addEventListener)document.addEventListener('DOMContentLoaded',c);else{var e=document.onreadystatechange||function(){};document.onreadystatechange=function(b){e(b);'loading'!==document.readyState&&(document.onreadystatechange=e,c())}}}})();