{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T00:51:42Z","timestamp":1775955102622,"version":"3.50.1"},"update-to":[{"DOI":"10.12688\/gatesopenres.13052.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2019,11,19]],"date-time":"2019-11-19T00:00:00Z","timestamp":1574121600000}}],"reference-count":25,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2019,11,19]],"date-time":"2019-11-19T00:00:00Z","timestamp":1574121600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/R015600\/1"],"award-info":[{"award-number":["MR\/R015600\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000278","name":"Department for International Development","doi-asserted-by":"publisher","award":["MR\/R015600\/1"],"award-info":[{"award-number":["MR\/R015600\/1"]}],"id":[{"id":"10.13039\/501100000278","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["OPP1184344"],"award-info":[{"award-number":["OPP1184344"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["OPP1129535"],"award-info":[{"award-number":["OPP1129535"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Schistosomiasis Consortium for Operational Research"},{"name":"Childrens\u2019 Investment Fund Foundation UK"}],"content-domain":{"domain":["gatesopenresearch.org"],"crossmark-restriction":false},"short-container-title":["Gates Open Res"],"abstract":"<ns4:p>\n                    Schistosomiasis remains one of the neglected tropical diseases (NTDs) impacting millions of people around the world. The World Health Organization (WHO) recently proposed a goal of elimination as a public health problem (EPHP) for schistosomiasis to be reached by 2030. Current WHO treatment guidelines for achieving EPHP focus on targeting school-aged children. The NTD Modelling Consortium has developed mathematical models to study schistosomiasis transmission dynamics and the impact of control measures. Our modelling insights on\n                    <ns4:italic>Schistosoma mansoni<\/ns4:italic>\n                    have shown that EPHP is likely to be attainable in low to moderate prevalence settings using the current guidelines. However, as prevalence rises within high prevalence settings, EPHP is less likely to be achieved unless both school-aged children and adults are treated (with coverage levels increasing with the adult burden of infection). We highlight the challenges that are faced by treatment programmes, such as non-adherence to treatment and resurgence, which can hinder progress towards achieving and maintaining EPHP. Additionally, even though EPHP may be reached, prevalence can still be high due to persisting infections. Therefore, without interruption of transmission, treatment will likely have to continue to maintain EPHP. Further modelling work is being carried out, including extending our results to\n                    <ns4:italic>S. haematobium<\/ns4:italic>\n                    . By providing these modelling insights, we aim to inform discussions on the goals and treatment guidelines for schistosomiasis.\n                  <\/ns4:p>","DOI":"10.12688\/gatesopenres.13052.2","type":"journal-article","created":{"date-parts":[[2019,11,19]],"date-time":"2019-11-19T11:45:22Z","timestamp":1574163922000},"page":"1517","update-policy":"https:\/\/doi.org\/10.12688\/gatesopenres.crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Insights from quantitative and mathematical modelling on the proposed WHO 2030 goal for schistosomiasis"],"prefix":"10.12688","volume":"3","author":[{"name":"NTD Modelling Consortium Schistosomiasis Group","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2560","published-online":{"date-parts":[[2019,11,19]]},"reference":[{"key":"ref-1","article-title":"Update on the global status of implementation of preventive chemotherapy 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programmes","year":"2011"},{"key":"ref-6","article-title":"Accelerating Progress for Schistosomiasis Control and Elimination Post-2020","year":"2019"},{"key":"ref-7","doi-asserted-by":"publisher","first-page":"S245-S252","DOI":"10.1093\/cid\/ciy001","article-title":"Are We on Our Way to Achieving the 2020 Goals for Schistosomiasis Morbidity Control Using Current World Health Organization Guidelines?","volume":"66","author":"J Toor","year":"2018","journal-title":"Clin Infect Dis."},{"key":"ref-8","doi-asserted-by":"publisher","first-page":"29-37","DOI":"10.1016\/j.epidem.2017.02.003","article-title":"A comparison of two mathematical models of the impact of mass drug administration on the transmission and control of schistosomiasis.","volume":"18","author":"J Truscott","year":"2017","journal-title":"Epidemics."},{"key":"ref-9","article-title":"Bench aids for the diagnosis of intestinal parasites","year":"1994"},{"key":"ref-10","doi-asserted-by":"publisher","first-page":"e0006717","DOI":"10.1371\/journal.pntd.0006717","article-title":"The design of schistosomiasis monitoring and evaluation programmes: The importance of collecting adult data to inform treatment strategies for Schistosoma mansoni.","volume":"12","author":"J Toor","year":"2018","journal-title":"PLoS Negl Trop Dis."},{"key":"ref-11","doi-asserted-by":"publisher","DOI":"10.3390\/tropicalmed3040111","article-title":"Low Praziquantel Treatment Coverage for Schistosoma mansoni in Mayuge District, Uganda, Due to the Absence of Treatment Opportunities, Rather Than Systematic Non-Compliance.","volume":"3","author":"M Adriko","year":"2018","journal-title":"Trop Med Infect Dis."},{"key":"ref-12","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1186\/s13071-017-2141-5","article-title":"Evaluating the variation in the projected benefit of community-wide mass treatment for schistosomiasis: Implications for future economic evaluations.","volume":"10","author":"H Turner","year":"2017","journal-title":"Parasit Vectors."},{"key":"ref-13","doi-asserted-by":"publisher","first-page":"e0005599","DOI":"10.1371\/journal.pntd.0005599","article-title":"Optimising cluster survey design for planning schistosomiasis preventive chemotherapy.","volume":"11","author":"S Knowles","year":"2017","journal-title":"PLoS Negl Trop Dis."},{"key":"ref-14","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1186\/s13071-017-2580-z","article-title":"Understanding the relationship between egg- and antigen-based diagnostics of Schistosoma mansoni infection pre- and post-treatment in Uganda.","volume":"11","author":"J Prada","year":"2018","journal-title":"Parasit Vectors."},{"key":"ref-15","doi-asserted-by":"publisher","first-page":"e0006941","DOI":"10.1371\/journal.pntd.0006941","article-title":"Translating preventive chemotherapy prevalence thresholds for Schistosoma mansoni from the Kato-Katz technique into the point-of-care circulating cathodic antigen diagnostic test.","volume":"12","author":"O Barenbold","year":"2018","journal-title":"PLoS Negl Trop Dis."},{"key":"ref-16","doi-asserted-by":"publisher","first-page":"e0006102","DOI":"10.1371\/journal.pntd.0006102","article-title":"Interpreting ambiguous 'trace' results in Schistosoma mansoni CCA Tests: Estimating sensitivity and specificity of ambiguous results with no gold standard.","volume":"11","author":"M Clements","year":"2017","journal-title":"PLoS Negl Trop Dis."},{"key":"ref-17","article-title":"Determining post-treatment surveillance criteria for predicting the elimination of Schistosoma mansoni transmission.","author":"J Toor","journal-title":"Parasit Vectors."},{"key":"ref-18","doi-asserted-by":"publisher","first-page":"435-443","DOI":"10.1016\/j.pt.2017.01.007","article-title":"Economic Considerations for Moving beyond the Kato-Katz Technique for Diagnosing Intestinal Parasites As We Move Towards Elimination.","volume":"33","author":"H Turner","year":"2017","journal-title":"Trends Parasitol."},{"key":"ref-19","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1186\/s13071-016-1311-1","article-title":"Compliance with anthelmintic treatment in the neglected tropical diseases control programmes: a systematic review.","volume":"9","author":"K Shuford","year":"2016","journal-title":"Parasit Vectors."},{"key":"ref-20","doi-asserted-by":"publisher","first-page":"1151-1159","DOI":"10.1093\/cid\/ciw506","article-title":"Reduced Efficacy of Praziquantel Against Schistosoma mansoni Is Associated With Multiple Rounds of Mass Drug Administration.","volume":"63","author":"T Crellen","year":"2016","journal-title":"Clin Infect Dis."},{"key":"ref-21","doi-asserted-by":"publisher","DOI":"10.3390\/tropicalmed4010030","article-title":"Elimination of Schistosomiasis Mekongi from Endemic Areas in Cambodia and the Lao People's Democratic Republic: Current Status and Plans.","volume":"4","author":"V Khieu","year":"2019","journal-title":"Trop Med Infect Dis."},{"key":"ref-22","doi-asserted-by":"publisher","first-page":"e1005098","DOI":"10.1371\/journal.ppat.1005098","article-title":"Hybridization in Parasites: Consequences for Adaptive Evolution, Pathogenesis, and Public Health in a Changing World.","volume":"11","author":"K King","year":"2015","journal-title":"PLoS Pathog."},{"key":"ref-23","doi-asserted-by":"publisher","first-page":"1613-1623","DOI":"10.1017\/S0031182017000014","article-title":"One hundred years of neglect in paediatric schistosomiasis.","volume":"144","author":"A Bustinduy","year":"2017","journal-title":"Parasitology."},{"key":"ref-24","doi-asserted-by":"publisher","first-page":"e0006484","DOI":"10.1371\/journal.pntd.0006484","article-title":"Schistosomiasis in Africa: Improving strategies for long-term and sustainable morbidity control.","volume":"12","author":"M French","year":"2018","journal-title":"PLoS Negl Trop Dis."},{"key":"ref-25","doi-asserted-by":"publisher","first-page":"e0006758","DOI":"10.1371\/journal.pntd.0006758","article-title":"Predicted short and long-term impact of deworming and water, hygiene, and sanitation on transmission of soil-transmitted helminths.","volume":"12","author":"L Coffeng","year":"2018","journal-title":"PLoS Negl Trop Dis."}],"container-title":["Gates Open Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/gatesopenresearch.org\/articles\/3-1517\/v2\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/gatesopenresearch.org\/articles\/3-1517\/v2\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/gatesopenresearch.org\/articles\/3-1517\/v2\/iparadigms","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,11,19]],"date-time":"2019-11-19T11:45:28Z","timestamp":1574163928000},"score":1,"resource":{"primary":{"URL":"https:\/\/gatesopenresearch.org\/articles\/3-1517\/v2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11,19]]},"references-count":25,"URL":"https:\/\/doi.org\/10.12688\/gatesopenres.13052.2","relation":{"has-review":[{"id-type":"doi","id":"10.21956\/gatesopenres.14237.r28258","asserted-by":"object"}]},"ISSN":["2572-4754"],"issn-type":[{"value":"2572-4754","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,11,19]]},"assertion":[{"value":"Indexed","URL":"https:\/\/gatesopenresearch.org\/articles\/3-1517\/v2#article-reports","order":0,"name":"referee-status","label":"Referee status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.21956\/gatesopenres.14179.r27699, W. Evan Secor, Parasitic Diseases Branch, Division of Parasitic Diseases and Malaria, Centers for Disease Control and Prevention, Atlanta, GA, USA, 04 Sep 2019, version 1, indexed","URL":"https:\/\/gatesopenresearch.org\/articles\/3-1517\/v1#referee-response-27699","order":0,"name":"referee-response-27699","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Jaspreet Toor<\/b>; \n<i>Posted: 15 Nov 2019<\/i>; We thank Evan for his feedback and agree with the concerns raised regarding the current WHO definition of EPHP. We have added more about how this current definition is limited in terms of its relationship to the reduction of schistosomiasis-associated morbidity. Further modelling will be done following revision of the goal as this may impact our recommended treatment strategies.  The following has been added in the background section: \u201cThere is uncertainty around how reliable the current WHO definition of EPHP is for estimating a reduction in schistosomiasis-related morbidity as lower intensity infections may also be associated with significant morbidity\n<sup> 3<\/sup>. Further modelling will be required following revision of this goal by WHO as this may impact our recommended treatment strategies.\u201d","URL":"https:\/\/gatesopenresearch.org\/articles\/3-1517\/v2#referee-comment-3242","order":1,"name":"referee-comment-3242","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.21956\/gatesopenres.14179.r27700, Stefanie Knopp, Swiss Tropical and Public Health Institute, Basel, Switzerland, 19 Sep 2019, version 1, indexed","URL":"https:\/\/gatesopenresearch.org\/articles\/3-1517\/v1#referee-response-27700","order":2,"name":"referee-response-27700","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Jaspreet Toor<\/b>; \n<i>Posted: 15 Nov 2019<\/i>; \n<i>We thank Stefanie for her comments and have responded to them in more detail below.<\/i>\n<b>Summary:<\/b>In this Open Letter article the authors reflect on results from quantitative and mathematical modelling that aimed to determine the impact of mass drug administration on the transmission and control of schistosomiasis and the impact of coverage in school-aged and adult populations to achieve elimination as public health problem (defined here as &lt;1% heavy intensity infections in school-aged children) depending on the prevalence level. Challenges that schistosomiasis control programmes might face when they move towards or have achieved elimination as public health problem are presented. With the article, the authors aim to inform discussions on the WHO goals and treatment guidelines for schistosomiasis.The modelling results provide important insights into whether, when and how the prevalence of schistosomiasis can be reduced and thus can well contribute to inform WHO guidelines. However, as the article is currently presented, there seems to be confusion of what the currently published (until 17.9.2019) WHO guidelines recommend and for what level of control and elimination. The authors indicate mass drug administration in school-aged children as the intervention recommended by WHO to reach elimination as public health problem. To my understanding, WHO currently recommends to \u201cadjust preventive chemotherapy and to use additional complementary public-health interventions\u201d for reaching elimination as a public health problem (Reference 4 of the article). Also, the Global Schistosomiasis Alliance (GSA) provided invited feedback on the new proposed WHO goals for schistosomiasis post 2020. The goal proposed by WHO on April 10, 2019 was: &quot;Elimination as a public health problem; Criteria to measure the achievement of the goal: Proportion of heavy intensity schistosomiasis infections &lt;1%)&quot;. The feedback from GSA on May 2nd, 2019 was &quot;\u2026the GSA strongly supports the proposal of the ambitious goal of interruption of transmission in selected countries and an interim and complementary goal of reducing the global burden of schistosomiasis disease\u2026\u201d. It would be good if the authors can clarify on the guidelines and their actual content and also refer more to interruption of transmission as the ultimate goal.Please also consider my specific comments to the manuscript and peer review form.\n<i>In the background section, the end goal of interruption of transmission has been stated more clearly (had previously been referred to as elimination of transmission throughout the letter). The last paragraph of the background section has been edited to make clearer that we have investigated current WHO guidelines in relation to the current EPHP goal. We have also noted in this paragraph that the current WHO goals and guidelines are under revision. Also see response * to comment below. <\/i>\n<b>Is the rationale for the Open Letter provided in sufficient detail?<\/b>The rationale is provided. However, the authors might consider adding some more details. Please see my following comments.\n<b>Does the article adequately reference differing views and opinions?<\/b>-My feeling is that some background on WHO guidelines for elimination as public health problem and interruption of transmission is missing or confused. Hence, it would be great if the authors can clarify that\/why they went for modelling of morbidity control approaches rather than considering what is recommended by WHO to achieve elimination of public health problem as per the strategic plan 2012-2020.\n<i>* As stated in the background section for morbidity control and EPHP, the WHO currently recommends 75% SAC treatment with treatment of adults at risk also being recommended. However, reported coverage shows that typically SAC are treated (ref 1); country programme managers have also said that they typically only have praziquantel available for SAC and not adults. Hence, we have followed treating 75% of SAC at the recommended MDA frequency (as detailed in background section; Table 1.1 recommended treatment strategy for schistosomiasis in WHO reference 4 of paper which is for morbidity control and EPHP). WHO reference 4a has also been added which states that the WHO target is to reach at least 75% SAC.<\/i>-Moreover, there is a recent trial that underlines that in a mostly low prevalence setting, 5 years of biannual MDA are not sufficient to reach elimination as a public health problem in all sentinel sites and to achieve interruption of transmission (Knopp et al., 2019a\n<sup>1<\/sup>, Knopp et al., 2019b\n<sup>2<\/sup>). Additional operational research studies were published by members of the Schistosomiasis Consortium for Operational Research and Evaluation on controlling morbidity with different MDA approaches. The results and conclusions could be discussed in this letter in relation to the modelling results.\n<i>** We are presenting these results as modelling insights and are aware of the risks faced by treatment programmes which will mean that our model recommendations are too optimistic if such risks are faced.We have clarified the model assumptions on coverage and adherence in the timelines section: \u201cHere, we have assumed treatment at random with full adherence at each round of MDA\u201d. We have added \u201cMore insights are needed on such risks as more intensified treatment strategies than those currently recommended here may be required if they are present\u201d to the risks faced by treatment programmes section (also within our biggest unknowns and risks in Table 1). <\/i>\n<b>Are all factual statements correct, and are statements and arguments made adequately supported by citations?<\/b>-The authors might want to consider the following comments:\n<b>Abstract:<\/b>1. The authors write: \u201cThe World Health Organization (WHO) recently proposed a goal of elimination as a public health problem (EPHP) for schistosomiasis to be reached by 2030. The authors might consider mentioning that WHO invited feedback and strategies for the proposed goals and that in the meantime in line with a consultation meeting, the Global Schistosomiasis Alliance (GSA) challenged that goal to some extent and responded to WHO as follows: \u201cGSA strongly supports the proposal of the ambitious goal of interruption of transmission in selected countries and an interim and complementary goal of reducing the global burden of schistosomiasis disease.\u201d (https:\/\/www.eliminateschisto.org\/news-events\/news\/gsa-consultation-meeting-accelerating-progress-for-schistosomiasis-control-and). In my view, the advice of the GSA on the proposed WHO goals should also be highlighted somewhere in this article. \u201cRecently\u201d could be replaced by the date so that the reader knows when these new goals were proposed and whether they are still up to date or not.\n<i>^ The following has been added to the background: \u201cIn May 2019, following a Global Schistosomiasis Alliance consultation meeting with its members and the WHO, there was support for the IOT goal with an interim and complementary goal of reducing the burden of schistosomiasis<sup>4b<\/sup>.\u201d Many of the abstract comments have been addressed throughout the text due to the word limit for the abstract.<\/i>2. The authors write: \u201cCurrent WHO treatment guidelines for achieving EPHP focus on targeting school-aged children\u201d. The authors might consider that in their strategic plan 2012-2020, WHO recommends to \u201cadjust preventive chemotherapy and to use additional complementary public-health interventions\u201d for reaching elimination as a public health problem\u201d (Reference 4 of the article). Hence, the available guidelines do not focus on targeting school-aged children only?\n<i>This is explained in the background section: \u201cMDA coverage has mainly focused on reaching 75% of SAC with treatment of adults at risk also recommended.\u201d We are using the WHO recommended treatment strategy shown in Table 1.1 and 2.2 in reference 4 and 4a of paper, respectively. This refers to treatment of SAC and adults at risk. To maintain clarity of which WHO guidelines we have analysed we are keeping the focus on targeting of SAC. Also see response * to comment above. <\/i>3. The authors write: \u201cThe NTD Modelling Consortium has developed mathematical models to study schistosomiasis transmission dynamics and the impact of control measures\u201d. The authors might consider highlighting which impact was measured (e.g. on prevalence or intensity) and to what control measures they refer (i.e. preventive chemotherapy or also measures such as snail control etc.).\n<i>Control measures investigated vary within the consortium. ICL looks at MDA, whereas, CWRU looks at MDA and snail control. We look at both prevalence and intensity. We feel this is too detailed to add to the abstract and have made it clear throughout the letter that we are focussing on MDA-only here. Further model details are available in the cited references, e.g. reference 6 in letter.<\/i>4. The authors write: \u201cOur modelling insights on Schistosoma mansoni have shown that EPHP is likely to be attainable in low to moderate prevalence settings using the current guidelines\u201d. It would be nice if the authors can define how they define low and moderate (i.e. provide a prevalence range). Moreover, which guidelines do they refer to? As indicated in my 2. comment, the strategic plan 2012-2020 recommends to \u201cadjust preventive chemotherapy and to use additional complementary public-health interventions\u201d. Rather referring to the guidelines (which ones?), the authors might consider referring to their modelling approach on preventive chemotherapy for school-aged children.\n<i>Using current WHO guidelines as stated. We use WHO definitions for low, moderate and high prevalence settings which are explained in the background section and tables 1-2.<\/i>5. The authors write: \u201cHowever, as prevalence rises within higher settings\u2026\u201d. The authors might consider defining \u201chigher setting\u201d. The sentence needs revision.\n<i>Edited to \u201cas prevalence rises within high prevalence settings\u2026\u201d Using WHO definition for high prevalence settings which is defined in background section and tables 1-2.<\/i>6.&nbsp;The authors write: \u201c\u2026(with coverage levels increasing with the adult burden of infection).\u201d It is not clear what the authors mean here. The authors might consider revising the part in brackets for more clarity.\n<i>This is explained in the insights gained from quantitative and mathematical modelling analyses section and shown in figure 1.<\/i>7. The authors write: \u201c\u2026hinder progress towards achieving and maintaining EPHP\u201d. The authors might consider that interruption of transmission has been suggested as goal, too (see my 1. Comment).\n<i>IOT has been mentioned in the background: \u201cThe WHO end goal for schistosomiasis is interruption of transmission (IOT) which is achieved once the incidence of infection is reduced to zero<sup>4, 4a<\/sup>.\u201d<\/i>8. \u201cEPHP\u201d should be defined at the beginning so that the reader better understands the following sentence \u201cAdditionally, even though EPHP may be reached, prevalence can still be high\u201d.\n<i>EPHP has been defined in Table 1 at its first mention in the letter.<\/i>9. The authors write: \u201cTherefore, without elimination of transmission, treatment will likely have to continue to maintain EPHP.\u201d The authors might consider defining \u201ctreatment\u201d. What treatment regimen do they have in mind? MDA?\n<i>Treatment has been left broad here as it does not mean only MDA necessarily, e.g. could include WASH as mentioned in the risks faced by treatment programmes section.<\/i>&nbsp;\n<b>Background:<\/b>1. The authors write: \u201cThe World Health Organization (WHO) has set goals of morbidity control and elimination as a public health problem (EPHP) for schistosomiasis to be reached by 2020 and 2025, respectively\n<sup>4<\/sup> (defined in Table 1).\u201d The authors might consider that the WHO also set goals for interruption of transmission in selected countries, to provide a complete picture of the goals set for 2020 and 2025.\n<i>This has been mentioned in the background: \u201cThe WHO end goal for schistosomiasis is interruption of transmission (IOT) which is achieved once the incidence of infection is reduced to zero<sup>4, 4a<\/sup>.\u201d <\/i>2. The authors write: \u201cThere are recommended WHO treatment guidelines for achieving these goals based on the prevalence in school-aged children\u201d. The authors might consider that in their strategic plan 2012-2020, the WHO recommends to \u201cadjust preventive chemotherapy and to use additional complementary public-health interventions\u201d for reaching elimination as a public health problem (World Health Organization, 2013\n<sup>3<\/sup>). Hence, in my view, the available guidelines do not focus on targeting school-aged children only. It seems to me that the authors refer to WHO recommendations for achieving morbidity control only, but not the actual guidelines for reaching elimination as public health problem. There are important differences in the approaches, which should be clarified.\n<i>See responses to abstract comment 2 and comment *.<\/i>3.&nbsp;The authors write: \u201cMathematical models of transmission dynamics and the impact of control interventions have been developed to inform decision makers on the optimal treatment strategies which are required for achieving the WHO goals\u201d. The authors might clarify which goals exactly they write about.\n<i>The last paragraph of the background section has been edited to make clearer that we have investigated current WHO guidelines in relation to the current EPHP goal.<\/i>4. The authors write: \u201cCurrently, the proposed 2030 goal for schistosomiasis is EPHP.\u201d The authors might consider mentioning that WHO invited feedback and strategies for the proposed goals and that in the meantime in line with a consultation meeting, the Global Schistosomiasis Alliance (GSA) challenged that goal to some extent and responded to WHO as follows: \u201cGSA strongly supports the proposal of the ambitious goal of interruption of transmission in selected countries and an interim and complementary goal of reducing the global burden of schistosomiasis disease.\u201d (https:\/\/www.eliminateschisto.org\/news-events\/news\/gsa-consultation-meeting-accelerating-progress-for-schistosomiasis-control-and).\n<i>See response ^.<\/i>5.&nbsp;The authors write: \u201cNote that the following sections focus on S. mansoni and Kato-Katz\u201d (as this is the currently recommended diagnostic technique). The authors might provide a reference for this recommendation of Kato-Katz.\n<i>Reference 6a has been added for this.<\/i>6.&nbsp;The authors write: \u201cAdditionally, the current WHO treatment guidelines have been investigated...\u201d. The authors might consider highlighting which guidelines exactly they investigated and for what (i.e. morbidity control or elimination as public health problem) and how, and provide a reference to the guidelines.\n<i>See response to comment 3 above, comment 2 in abstract and *.<\/i>7. The authors write: \u201c\u2026the currently recommended WHO guidelines (of 75% SAC-only treatment) are sufficient for achieving the EPHP goal for S. mansoni.\u201d As indicated in my previous comments, the current guidelines indicate that to achieve elimination of schistosomiasis as a public health problem, WHO recommends to \u201cadjust preventive chemotherapy and to use additional complementary public-health interventions\u201d (World Health Organization, 2013\n<sup>3<\/sup>). Hence, it remains unclear, why the authors stick to recommendations for morbidity control and not elimination as a public health problem?\n<i>See response to comment 2 in abstract and *.<\/i>8. The authors write: \u201cAs the burden of infection in adults relative to SAC increases\u2026\u201d. The authors might define burden. Is it measured in intensity, worm numbers, DALYs or something else?\n<i>The burden relates to the transmission intensity - The age-specific contact rates, i.e. transmission intensities by age group, were varied such that the adults have a low or high burden of infection relative to SAC. This has been clarified in the sentence referred to: \u201cAs the burden of infection (intensity of transmission) in adults relative to SAC increases\u2026\u201d<\/i>&nbsp;&nbsp;\n<b>Practical implications:<\/b>1. The authors write: \u201cEPHP is technically feasible in all settings within 10 years provided that the appropriate treatment strategy is used...\u201d. A recent study on S. haematobium in Zanzibar, a setting targeted for elimination as public health problem and interruption of transmission, showed that despite 5 years of bi-annual MDA in schoolchildren with high coverage and adults with moderate compliance, elimination as public health problem was not reached in all sentinel sites, probably due to heterogeneity in transmission and some remaining pockets with high transmission potential, where people got reinfected rapidly (Knopp et al., 2019a\n<sup>1<\/sup>, Knopp et al., 2019b\n<sup>2<\/sup>). The authors might consider validating their model based on available field data.\n<i>Agree, we are planning to do this. Our modelling insights here are assuming 100% adherence and coverage at random at each round of MDA (see response ** above).<\/i>2.&nbsp;The authors write: \u201cTo monitor and assess progress towards the EPHP goal, prevalence and infection intensity data are required from SAC (as the goal is defined by &lt;1% prevalence of heavy-intensity infections in SAC).\u201d The authors might consider adding a reference. When checking the proposed goals published by WHO at https:\/\/www.who.int\/neglected_diseases\/news\/NTD-Roadmap-targets-2021-2030.pdf?ua=1, I did not see any mention of \u201cSAC\u201c. The current guidelines define elimination as public health problem as \u201c&lt;1% heavy infection intensities in all sentinel sites\u201d (World Health Organization, 2013\n<sup>3<\/sup>).\n<i>*** We are referring to the current EPHP goal here as stated at the end of the background section. Defined in table 4.4 in reference 4a (reference has been added to letter) as heavy-intensity infections are measured in SAC.<\/i>3. The authors write: \u201cThe goal is currently assessed by averaging the prevalence measured in five schools randomly sampled within a district.\u201d Is measuring prevalence in 5 schools related to the modelling approach of the authors or is it a recommendation by WHO to? If the latter, the authors might consider providing a reference.\n<i>5 schools per district are frequently surveyed for mapping schistosomiasis. This has been edited to: \u201cThe goal is currently typically assessed by averaging the prevalence measured in five schools randomly sampled within a district<sup>10<\/sup>.\u201d<\/i>4.&nbsp;The authors write: \u201cPre-SAC can also be infected with schistosomiasis\u2026\u201d. The authors might consider that a patient is not infected with a disease but with the disease-causing agent, in this case schistosomes.\n<i>Corrected to schistosomes.<\/i>5.&nbsp;The authors write: \u201cDevelopment of a paediatric formulation of praziquantel for pre-SAC treatment would prevent this\u201d. The authors might consider that not only the development but finally only the large-scale application of the paediatric praziquantel would reduce a potential reservoir in PSAC.\n<i>We have not used our modelling analyses to determine the coverage at which paediatric praziquantel would need to be given in order to have an impact. Hence, we do not mention the scale of this.<\/i>6.&nbsp;The authors write: \u201cDue to remaining infections, it is highly likely that treatment will still be needed after achieving EPHP\u201d. Again, it would be nice if the authors can clarify what is meant with \u201ctreatment\u201d.\n<i>See response to abstract comment 9.<\/i>7.&nbsp;The authors write: \u201cTo alleviate the need for ongoing treatment and to prevent resurgence, EOT is required after reaching EPHP.\u201d The authors might consider indicating that this is\/was one of the goals of WHO for selected countries until 2025 and that also \u201cGSA strongly supports the proposal of the ambitious goal of interruption of transmission in selected countries\u201d.\n<i>In the background we state that IOT is the WHO end goal for schistosomiasis. Also see response ^.<\/i>8.&nbsp;The authors write: \u201cThe transition of treatment programmes from EPHP to EOT will require reassessment of the treatment strategy.\u201d The authors might consider clarifying if they indeed refer to treatment strategies only, or broader intervention strategies, i.e. including also snail control, WASH, behaviour change, surveillance-response, etc.\n<i>We are referring to MDA and broader intervention strategies. The following has been added to the sentence to clarify: \u201cwith consideration of additional interventions such as behaviour change and snail control.\u201d<\/i>\n<b>Table 1:<\/b>1. The authors write: \u201cElimination as a public health problem (EPHP): &lt;1% prevalence of heavy-intensity infections in SAC\u201d. Note that this is the current 2025 goal. To my knowledge, the current goal is not referring to SAC but sentinel sites?\n<i>See response ***.<\/i>2. The authors write: \u201cIn low to moderate prevalence settings (&lt;50% SAC prevalence prior to treatment), EPHP is likely to be achieved with 75% SAC-only treatment.\u201d For how many years is SAC needed to be treated?\n<i>Timelines to achieve EPHP are shown in Table 2.<\/i>\n<b>Priority questions:<\/b>  Validation of the models with real data from different prevalence and intensity settings could be one additional aim.  \n<i>We agree and this is part of our ongoing work. However, the priority questions listed here are those which have been identified in discussions with WHO.<\/i>","URL":"https:\/\/gatesopenresearch.org\/articles\/3-1517\/v2#referee-comment-3243","order":3,"name":"referee-comment-3243","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.21956\/gatesopenres.14179.r27696, Darin Evans, United States Agency for International Development  (USAID), Washington, DC, USA, 22 Oct 2019, version 1, indexed","URL":"https:\/\/gatesopenresearch.org\/articles\/3-1517\/v1#referee-response-27696","order":4,"name":"referee-response-27696","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Jaspreet Toor<\/b>; \n<i>Posted: 15 Nov 2019<\/i>; We thank Darin for his feedback and agree with the points raised. The following has been added in the background section: \u201cThere is uncertainty around how reliable the current WHO definition of EPHP is for estimating a reduction in schistosomiasis-related morbidity as lower intensity infections may also be associated with significant morbidity\n<sup>3<\/sup>.\u201d  The following has been added to the risks faced by treatment programmes section: \u201cDue to remaining infections, it is highly likely that treatment will still be needed to maintain control after achieving EPHP\n<sup>20a<\/sup>.\u201d","URL":"https:\/\/gatesopenresearch.org\/articles\/3-1517\/v2#referee-comment-3244","order":5,"name":"referee-comment-3244","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"JT, CF, JP, CHK, DH, GFM and RMA gratefully acknowledge funding of the NTD Modelling Consortium by the Bill and Melinda Gates Foundation [OPP1184344]. JT and RMA acknowledge joint Centre funding from the UK Medical Research Council and Department for International Development [MR\/R015600\/1]. This work was also supported by the Bill & Melinda Gates Foundation for research grant support via the DeWorm3 [OPP1129535] award to the Natural History Museum in London to RMA; the Childrens\u2019 Investment Fund Foundation (CIFF) UK and the Schistosomiasis Consortium for Operational Research and Evaluation based at the University of Georgia to CHK. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":6,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}