{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T05:10:49Z","timestamp":1772169049821,"version":"3.50.1"},"update-to":[{"DOI":"10.12688\/wellcomeopenres.16624.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,12,9]],"date-time":"2021-12-09T00:00:00Z","timestamp":1639008000000}}],"reference-count":27,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2021,12,9]],"date-time":"2021-12-09T00:00:00Z","timestamp":1639008000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000030","name":"Centers for Disease Control and Prevention Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000030","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32AI007044"],"award-info":[{"award-number":["T32AI007044"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["F32AI140511"],"award-info":[{"award-number":["F32AI140511"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"crossref","award":["212638"],"award-info":[{"award-number":["212638"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["wellcomeopenresearch.org"],"crossmark-restriction":false},"short-container-title":["Wellcome Open Res"],"abstract":"<ns3:p>\n                    <ns3:bold>Background:<\/ns3:bold>\n                    Cryptococcal antigen (CrAg) screening in individuals with advanced HIV reduces cryptococcal meningitis (CM) cases and deaths. The World Health Organization recently recommended increasing screening thresholds from CD4 \u2264100 cells\/\u00b5L to \u2264200 cells\/\u00b5L. CrAg screening at CD4 \u2264100 cells\/\u00b5L is cost-effective; however, the cost-effectiveness of screening patients with CD4 101\u2013200 cells\/\u00b5L requires evaluation.\n                  <\/ns3:p>\n                  <ns3:p>\n                    <ns3:bold>Methods:<\/ns3:bold>\n                    Using a decision analytic model with Botswana-specific cost and clinical estimates, we evaluated CrAg screening and treatment among individuals with CD4 counts of 101\u2013200 cells\/\u00b5L. We estimated the number of CM cases and deaths nationally and treatment costs without screening. For screening we modeled the number of CrAg tests performed, number of CrAg-positive patients identified, proportion started on pre-emptive fluconazole, CM cases and deaths. Screening and treatment costs were estimated and cost per death averted or disability-adjusted life year (DALY) saved compared with no screening.\n                  <\/ns3:p>\n                  <ns3:p>\n                    <ns3:bold>Results:<\/ns3:bold>\n                    Without screening, we estimated 142 CM cases and 85 deaths annually among individuals with CD4 101\u2013200 cells\/\u00b5L, with treatment costs of $368,982. With CrAg screening, an estimated 33,036 CrAg tests are performed, and 48 deaths avoided (1,017 DALYs saved).\u00a0 While CrAg screening costs an additional $155,601, overall treatment costs fall by $39,600 (preemptive and hospital-based CM treatment), yielding a net increase of $116,001. Compared to no screening, high coverage of CrAg screening and pre-emptive treatment for CrAg-positive individuals in this population avoids one death for $2440 and $114 per DALY saved. In sensitivity analyses assuming a higher proportion of antiretroviral therapy (ART)-na\u00efve patients (75% versus 15%), cost per death averted was $1472; $69 per DALY saved.\n                  <\/ns3:p>\n                  <ns3:p>\n                    <ns3:bold>Conclusions:<\/ns3:bold>\n                    CrAg screening for individuals with CD4 101\u2013200 cells\/\u00b5L was estimated to have a modest impact, involve additional costs, and be less cost-effective than screening populations with CD4 counts \u2264100 cells\/\u00b5L. Additional CrAg screening costs must be considered against other health system priorities.\n                  <\/ns3:p>","DOI":"10.12688\/wellcomeopenres.16624.2","type":"journal-article","created":{"date-parts":[[2021,12,9]],"date-time":"2021-12-09T11:35:09Z","timestamp":1639049709000},"page":"55","update-policy":"https:\/\/doi.org\/10.12688\/wellcomeopenres.crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Cost-effectiveness of cryptococcal antigen screening at CD4 counts of 101\u2013200 cells\/\u00b5L in Botswana"],"prefix":"10.12688","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8702-8393","authenticated-orcid":false,"given":"Mark W.","family":"Tenforde","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles","family":"Muthoga","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ponego","family":"Ponatshego","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia","family":"Ngidi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Madisa","family":"Mine","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Greg","family":"Greene","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7834-866X","authenticated-orcid":false,"given":"Alexander","family":"Jordan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tom","family":"Chiller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9322-2387","authenticated-orcid":false,"given":"Bruce A.","family":"Larson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1459-5554","authenticated-orcid":false,"given":"Joseph N.","family":"Jarvis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2560","published-online":{"date-parts":[[2021,12,9]]},"reference":[{"key":"ref-1","article-title":"Fact sheet - World AIDS day 2018"},{"key":"ref-2","doi-asserted-by":"publisher","first-page":"2223-30","DOI":"10.1097\/QAD.0000000000002627","article-title":"Advanced HIV disease in the Botswana combination prevention project: prevalence, risk factors, and outcomes.","volume":"34","author":"R Lebelonyane","year":"2020","journal-title":"AIDS."},{"key":"ref-3","article-title":"2016 integrated HIV clinical care 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Treatment of Cryptococcal Meningitis in Africa.","volume":"378","author":"S Molloy","year":"2018","journal-title":"N Engl J Med."},{"key":"ref-11","doi-asserted-by":"publisher","first-page":"1-10","DOI":"10.1111\/hiv.12951","article-title":"Utility of CD4 count measurement in the era of universal antiretroviral therapy: an analysis of routine laboratory data in Botswana.","volume":"22","author":"T Leeme","year":"2021","journal-title":"HIV Med."},{"key":"ref-12","doi-asserted-by":"publisher","first-page":"1635-1638","DOI":"10.1093\/cid\/ciaa899","article-title":"Outcomes of Reflex Cryptococcal Antigen (CrAg) Screening in Human Immunodeficiency Virus (HIV)-Positive Patients With CD4 Counts of 100-200 Cells\/\u00b5L in Botswana.","volume":"72","author":"M Tenforde","year":"2021","journal-title":"Clin Infect Dis."},{"key":"ref-13","article-title":"Cryptococcal antigen screening in Botswana, CD4 101-200","author":"M Tenforde","year":"2021"},{"key":"ref-14","doi-asserted-by":"publisher","first-page":"686-92","DOI":"10.1093\/cid\/cix872","article-title":"High Cryptococcal Antigen Titers in Blood are Predictive of Subclinical Cryptococcal Meningitis Among Human Immunodeficiency Virus-Infected Patients.","volume":"66","author":"R Wake","year":"2018","journal-title":"Clin Infect Dis."},{"key":"ref-15","doi-asserted-by":"publisher","first-page":"1745-1754","DOI":"10.1093\/cid\/ciaa356","article-title":"Prevalence and Sequelae of Cryptococcal Antigenemia in Antiretroviral Therapy-experienced Populations: An Evaluation of Reflex Cryptococcal Antigen Screening in Botswana.","volume":"72","author":"W Hurt","year":"2021","journal-title":"Clin Infect Dis."},{"key":"ref-16","doi-asserted-by":"publisher","first-page":"2126-9","DOI":"10.1093\/cid\/cix613","article-title":"High Dose Fluconazole Monotherapy is Inadequate for CSF Cryptococcal Antigen Positive HIV-infected Persons in an Ethiopian CrAg Screening 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J HIV Med."}],"container-title":["Wellcome Open Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/wellcomeopenresearch.org\/articles\/6-55\/v2\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/wellcomeopenresearch.org\/articles\/6-55\/v2\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/wellcomeopenresearch.org\/articles\/6-55\/v2\/iparadigms","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,18]],"date-time":"2022-01-18T03:50:13Z","timestamp":1642477813000},"score":1,"resource":{"primary":{"URL":"https:\/\/wellcomeopenresearch.org\/articles\/6-55\/v2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,9]]},"references-count":27,"URL":"https:\/\/doi.org\/10.12688\/wellcomeopenres.16624.2","relation":{"has-review":[{"id-type":"doi","id":"10.21956\/wellcomeopenres.19327.r47575","asserted-by":"subject"},{"id-type":"doi","id":"10.21956\/wellcomeopenres.19327.r47575","asserted-by":"object"}]},"ISSN":["2398-502X"],"issn-type":[{"value":"2398-502X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,9]]},"assertion":[{"value":"Indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/6-55\/v2#article-reports","order":0,"name":"referee-status","label":"Referee status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.21956\/wellcomeopenres.18328.r43398, Elizabeth Nalintya, Infectious Diseases Institute, College of Health Sciences, Makerere University, Kampala, Uganda, 28 Apr 2021, version 1, 1 approved, 1 approved with reservations","URL":"https:\/\/wellcomeopenresearch.org\/articles\/6-55\/v1#referee-response-43398","order":0,"name":"referee-response-43398","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.21956\/wellcomeopenres.19327.r47575, Stephanie Popping, Department of Viroscience, Erasmus MC, Rotterdam, The Netherlands, 18 Jan 2022, version 2, indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/6-55\/v2#referee-response-47575","order":1,"name":"referee-response-47575","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"We acknowledge Wellcome Trust funding to CM through a Master\u2019s Fellowship in Public Health and Tropical Medicine (grant 212638\/Z\/18\/Z). Additional funding for this work was from the U.S. National Institutes of Health (NIH) National Institute of Allergy and Infectious Diseases (NIAID) [grants T32AI007044 and F32AI140511] to MWT, and the U.S. Centers for Disease Control and Prevention (CDC) Foundation to BL and JNJ. This project was made possible through an agreement with the CDC Foundation with financial support provided by Pfizer Inc. JNJ reports additional support from the Penn Center for AIDS Research (CFAR), a NIH-funded program (grant P30AI045008), and the U.K. National Health Service (NHS) National Institute for Health Research (NIHR) using Official Development Assistance (ODA) funding through a Global Health Professorship (grant RP-2017-08-ST2-012). The views expressed are those of the authors and not necessarily the official position of CDC, the NHS, NIHR, the Department of Health and Social Care, or other funding entities. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":2,"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"}]}}