{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T12:46:20Z","timestamp":1768481180887,"version":"3.49.0"},"reference-count":50,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2023,10,19]],"date-time":"2023-10-19T00:00:00Z","timestamp":1697673600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100019833","name":"World Health Organization Centre for Health Development","doi-asserted-by":"publisher","award":["WHO-Afro-TDR small grants 2018"],"award-info":[{"award-number":["WHO-Afro-TDR small grants 2018"]}],"id":[{"id":"10.13039\/100019833","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017201","name":"Fundaci\u00f3n Mutual M\u00e9dica","doi-asserted-by":"publisher","award":["Beca Mutual Medica 2018-66"],"award-info":[{"award-number":["Beca Mutual Medica 2018-66"]}],"id":[{"id":"10.13039\/100017201","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\"><jats:title>Introduction<\/jats:title><jats:p>In low-resource settings, anaemia is a very common condition. Identification of anaemia aetiologies remains challenging due to the lack of diagnostic tools and expertise. We aimed to improve anaemia diagnostics using peripheral blood smear (PBS) with remote interpretation in people living with HIV (PLHIV) with moderate to severe anaemia.<\/jats:p><\/jats:sec><jats:sec id=\"sec002\"><jats:title>Methods<\/jats:title><jats:p>We conducted a prospective study nested within the Kilombero and Ulanga Antiretroviral Cohort, including non-pregnant PLHIV aged \u226518 years presenting with moderate (haemoglobin 7.0\u20139.9 g\/dl) or severe (&lt;7.0 g\/dl) anaemia at any visit from January 2019 to December 2020. For each participant, ten PBS images, full blood count and clinical details were shared with a haematologist for remote interpretation (enhanced care). Identification of anaemia etiologies and potential impact on treatment was compared between enhanced and standard care.<\/jats:p><\/jats:sec><jats:sec id=\"sec003\"><jats:title>Results<\/jats:title><jats:p>Among 400 PLHIV with moderate to severe anaemia, 349 (87%) were female, median age was 40 years (interquartile range (IQR) 35\u201346)), 65 (17%) had a body mass index &lt;18.5 kg\/m<jats:sup>2<\/jats:sup>, 215 (54%) had HIV WHO stage III\/IV, 79 (20%) had a CD4 cell count &lt;200 cells\/\u03bcl and 317 (89%) had HIV viral load &lt;100 copies\/ml. Severe anaemia was diagnosed in 84 (21%). Suspected multiple aetiologies were documented more frequently by enhanced care compared to standard care 267 (67%) vs 20 (5%); p&lt;0.001. Suspected iron deficiency was the most frequent aetiology (n = 337; 84%), followed by chronic disease (n = 199; 50%), folate\/vitamin B12 deficiency (n = 78; 20%) and haemoglobinopathy (n = 83; 21%). In 272 participants (68%), enhanced care revealed additional clinically relevant findings with impact on the treatment recommendation.<\/jats:p><\/jats:sec><jats:sec id=\"sec004\"><jats:title>Conclusion<\/jats:title><jats:p>Remote interpretation of PBS combined with clinical information and blood cell count results can provide insights to the suspected aetiological diagnosis of moderate and severe anaemia in rural low-resource settings and impact specific treatment.<\/jats:p><\/jats:sec>","DOI":"10.1371\/journal.pone.0293084","type":"journal-article","created":{"date-parts":[[2023,10,19]],"date-time":"2023-10-19T17:48:05Z","timestamp":1697737685000},"page":"e0293084","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Improving anaemia diagnosis using peripheral blood smear with remote interpretation in adults living with HIV with moderate to severe anaemia: A prospective study nested within the Kilombero and Ulanga antiretroviral cohort"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4414-3017","authenticated-orcid":true,"given":"Vanesa","family":"Anton-Vazquez","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dorcas","family":"Mnzava","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James","family":"Okuma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Slyakus","family":"Mlembe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Lo Riso","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7337-9731","authenticated-orcid":true,"given":"Jose Maria","family":"Sanchez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Ndege","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aneth","family":"Vedastus Kalinjuma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Namvua","family":"Kimera","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Eichenberger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanni Jacopo","family":"Nicoletti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Herieth","family":"Wilson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fiona","family":"Vanobberghen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maja","family":"Weisser","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"on behalf of the KIULARCO Study Group","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2023,10,19]]},"reference":[{"issue":"Suppl 7A","key":"pone.0293084.ref001","doi-asserted-by":"crossref","first-page":"27s","DOI":"10.1016\/j.amjmed.2003.12.010","article-title":"Prevalence and outcomes of anemia in individuals with human immunodeficiency virus: a systematic review of the literature","volume":"116","author":"PS Belperio","year":"2004","journal-title":"The American journal of medicine"},{"key":"pone.0293084.ref002","doi-asserted-by":"crossref","first-page":"157","DOI":"10.4066\/AMJ.2012.100","article-title":"Haematological changes in HIV infection with correlation to CD4 cell count","volume":"5","author":"S Parinitha","year":"2012","journal-title":"The Australasian Medical Journal"},{"issue":"8","key":"pone.0293084.ref003","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1097\/00002030-199905280-00010","article-title":"Anaemia is an independent predictive marker for clinical prognosis in HIV-infected patients from across Europe","volume":"28","author":"A Mocroft","year":"1999","journal-title":"AIDS (London, England)."},{"issue":"1","key":"pone.0293084.ref004","first-page":"145","article-title":"EuroSIDA Study Group. A clinically prognostic scoring system for patients receiving highly active antiretroviral therapy: results from the EuroSIDA study.","volume":"186","author":"JD Lundgren","year":"2002","journal-title":"J. The Journal of infectious diseases"},{"issue":"1","key":"pone.0293084.ref005","first-page":"13","article-title":"Anaemia in persons with HIV infection: prognostic marker and contributor to morbidity","volume":"4","author":"G. Moyle","year":"2002","journal-title":"AIDS Rev"},{"key":"pone.0293084.ref006","first-page":"7075601","article-title":"Prevalence and Risk Factors of Mortality among Adult HIV Patients Initiating ART in Rural Setting of HIV Care and Treatment Services in North Western Tanzania: A Retrospective Cohort Study","volume":"2017","author":"DW Gunda","year":"2017","journal-title":"J Sex Transm Dis."},{"key":"pone.0293084.ref007","doi-asserted-by":"crossref","first-page":"101283","DOI":"10.1016\/j.eclinm.2022.101283","article-title":"Prevalence of anemia among people living with HIV: A systematic review and meta-analysis.","volume":"44","author":"G Cao","year":"2022","journal-title":"EClinicalMedicine"},{"issue":"2","key":"pone.0293084.ref008","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1093\/inthealth\/ihaa036","article-title":"Anemia and thrombocytopenia in people living with HIV\/AIDS: a narrative literature review","volume":"13","author":"A Marchionatti","year":"2021","journal-title":"Int Health"},{"issue":"6","key":"pone.0293084.ref009","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1177\/135965350601100612","article-title":"Prevalence, incidence and predictors of severe anaemia with zidovudine-containing regimens in African adults with HIV infection within the DART trial","volume":"11","author":"F Ssali","year":"2006","journal-title":"Antivir Ther"},{"issue":"1","key":"pone.0293084.ref010","first-page":"301","article-title":"Epidemiology of anemia in human immunodeficiency virus (HIV)-infected persons: results from the multistate adult and adolescent spectrum of HIV disease surveillance project","volume":"91","author":"PS Sullivan","year":"1998","journal-title":"Blood Conference: 51st Annual Meeting of the American Society of Hematology, ASH New Orleans, LA United States Conference Publication"},{"issue":"32","key":"pone.0293084.ref011","article-title":"Prevalence of anemia and its associated factors in human immuno deficiency virus infected adult individuals in Ethiopia. A systematic review and meta-analysis","volume":"18","author":"A Negesse","year":"2018","journal-title":"BMC Hematol"},{"issue":"1","key":"pone.0293084.ref012","first-page":"2","article-title":"Prevalence of anaemia and immunological markers among ghanaian HAART-na\u00efve HIV-patients and those on HAART.","volume":"11","author":"WK Owiredu","year":"2011","journal-title":"Afr Health Sci"},{"issue":"4","key":"pone.0293084.ref013","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1017\/S1368980008002401","article-title":"Worldwide prevalence of anaemia, WHO vitamin and mineral nutrition information system 1993\u20132005","volume":"12","author":"E McLean","year":"2009","journal-title":"Public Health Nutrition"},{"issue":"11","key":"pone.0293084.ref014","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1186\/1471-2334-11-190","article-title":"Antiretroviral treatment reverses HIV-associated anemia in rural Tanzania","volume":"11","author":"A Johannessen","year":"2011","journal-title":"BMC Infect Dis"},{"issue":"1","key":"pone.0293084.ref015","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4314\/thrb.v11i1.43242","article-title":"Prevalence of anaemia among HIV-infected patients in Benin City, Nigeria.","volume":"11","author":"R Omoregie","year":"2009","journal-title":"Tanzan J Health Res"},{"issue":"1","key":"pone.0293084.ref016","first-page":"1","article-title":"Prevalence of anaemiabefore and after the initiation of antiretroviral therapy at ARTcentre of Hawassa University Referral Hospital, Hawassa, SouthEthiopia.","volume":"3","author":"D Deresse","year":"2013","journal-title":"Scholarly Journal of Medicine"},{"key":"pone.0293084.ref017","doi-asserted-by":"crossref","first-page":"26","DOI":"10.11604\/pamj.2016.23.26.8268","article-title":"Magnitude and correlates of moderate to severe anemia among adult HIV patients receiving first line HAART in Northwestern Tanzania: a cross sectional clinic based study.","volume":"23","author":"DW Gunda","year":"2016","journal-title":"The Pan African medical journal"},{"issue":"6","key":"pone.0293084.ref018","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1097\/QAD.0000000000002171","article-title":"Age-related comorbidities and mortality in people living with HIV in rural Tanzania","volume":"33","author":"S Albrecht","year":"2019","journal-title":"AIDS (London, England)."},{"issue":"2","key":"pone.0293084.ref019","doi-asserted-by":"crossref","first-page":"193","DOI":"10.5588\/ijtld.15.0558","article-title":"Anaemia in patients with HIV-associated TB: relative contributions of anaemia of chronic disease and iron deficiency.","volume":"20","author":"AD Kerkhoff","year":"2016","journal-title":"The international journal of tuberculosis and lung disease: the official journal of the International Union against Tuberculosis and Lung Disease"},{"key":"pone.0293084.ref020","first-page":"123","article-title":"Malaria and HIV coinfection in sub-Saharan Africa: prevalence, impact, and treatment strategies","volume":"9","author":"TE Kwenti","year":"2018","journal-title":"Res Rep Trop Med"},{"issue":"1","key":"pone.0293084.ref021","doi-asserted-by":"crossref","first-page":"36","DOI":"10.4269\/ajtmh.2009.80.36","article-title":"Geophagy (Soil-eating) in relation to Anemia and Helminth infection among HIV-infected pregnant women in Tanzania","volume":"80","author":"K Kawai","year":"2009","journal-title":"The American journal of tropical medicine and hygiene"},{"issue":"1","key":"pone.0293084.ref022","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1186\/s12875-020-01241-7","article-title":"A new diagnostic work-up for defining anemia etiologies: a cohort study in patients \u2265 50 years in general practices.","volume":"21","author":"A Schop","year":"2020","journal-title":"BMC Fam Pract"},{"issue":"2","key":"pone.0293084.ref023","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1097\/01.qai.0000134759.01684.27","article-title":"Impact of highly active antiretroviral therapy on anemia and relationship between anemia and survival in a large cohort of HIV-infected women: Women\u2019s Interagency HIV Study","volume":"1","author":"K Berhane","year":"2004","journal-title":"Journal of acquired immune deficiency syndromes (1999)."},{"issue":"1","key":"pone.0293084.ref024","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/1758-2652-15-5","article-title":"Short-term risk of anaemia following initiation of combination antiretroviral treatment in HIV-infected patients in countries in sub-Saharan Africa, Asia-Pacific, and central and South America","volume":"15","author":"J Zhou","year":"2012","journal-title":"J Int AIDS Soc"},{"issue":"5","key":"pone.0293084.ref025","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1056\/NEJMra043442","article-title":"Diagnosis from the blood smear","volume":"353","author":"BJ Bain","year":"2005","journal-title":"The New England journal of medicine"},{"issue":"4","key":"pone.0293084.ref026","first-page":"175","article-title":"Physician review of the peripheral blood smear: When and Why An opinion","volume":"7","author":"P Peterson","year":"2001","journal-title":"Laboratory Hematology"},{"key":"pone.0293084.ref027","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1111\/ijlh.12667","article-title":"Does morphology matter in 2017? An approach to morphologic clues in non-neoplastic blood and bone marrow disorders","volume":"39","author":"DS Chabot-Richards","year":"2017","journal-title":"International Journal of Laboratory Hematology"},{"key":"pone.0293084.ref028","first-page":"w14485","article-title":"Cohort profile: The Kilombero and Ulanga Antiretroviral Cohort (KIULARCO)\u2014A prospective HIV cohort in rural Tanzania.","volume":"147","author":"E Letang","year":"2017","journal-title":"Swiss medical weekly"},{"issue":"7","key":"pone.0293084.ref029","doi-asserted-by":"crossref","first-page":"e0180983","DOI":"10.1371\/journal.pone.0180983","article-title":"A decade of HIV care in rural Tanzania: Trends in clinical outcomes and impact of clinic optimisation in an open, prospective cohort","volume":"12","author":"F Vanobberghen","year":"2017","journal-title":"PLoS One"},{"key":"pone.0293084.ref030","volume-title":"Hemoglobin data in DHS Surveys: Intrinsic variation and measurement error.","author":"T Pullum","year":"2017"},{"issue":"8","key":"pone.0293084.ref031","first-page":"1039","article-title":"Guidelines for setting up an external quality assessment scheme for blood smear interpretation. Part II: survey preparation, statistical evaluation and reporting","volume":"44","author":"JL Vives Corrons","year":"2006","journal-title":"Clinical chemistry and laboratory medicine"},{"issue":"3","key":"pone.0293084.ref032","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1111\/ijlh.12327","article-title":"ICSH recommendations for the standardization of nomenclature and grading of peripheral blood cell morphological features","volume":"37","author":"L Palmer","year":"2015","journal-title":"International journal of laboratory hematology"},{"key":"pone.0293084.ref033","article-title":"Best practice recommendations for implementing digital pathology January 2018.","author":"S Cross","year":"2018","journal-title":"The Royal College of Pathologists website"},{"key":"pone.0293084.ref034","volume-title":"Guidelines for Patholoigists.","author":"World Health Organization (WHO) Telepathology.","year":"2009"},{"key":"pone.0293084.ref035","article-title":"BMJ best practice, evaluation of anemia","author":"R. Zaiden","year":"2019","journal-title":"BMJ publishing group"},{"key":"pone.0293084.ref036","author":"Centre HaSCI","year":"2016","edition":"5"},{"issue":"5","key":"pone.0293084.ref037","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1182\/blood-2013-06-508325","article-title":"A systematic analysis of global anemia burden from 1990 to 2010","volume":"123","author":"NJ Kassebaum","year":"2014","journal-title":"Blood"},{"key":"pone.0293084.ref038","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1056\/NEJMra041809","article-title":"Anaemia of chronic disease","volume":"352","author":"G Weiss","year":"2005","journal-title":"N Engl J Med"},{"issue":"4","key":"pone.0293084.ref039","doi-asserted-by":"crossref","first-page":"359","DOI":"10.3329\/jhpn.v28i4.6042","article-title":"Prevalence of anaemia, deficiencies of iron and folic acid and their determinants in Ethiopian women.","volume":"28","author":"J. Haidar","year":"2010","journal-title":"J Health Popul Nutr"},{"issue":"1","key":"pone.0293084.ref040","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1111\/nyas.14092","article-title":"Anemia epidemiology, pathophysiology, and etiology in low- and middle-income countries","volume":"1450","author":"CM Chaparro","year":"2019","journal-title":"Ann N Y Acad Sci"},{"issue":"1","key":"pone.0293084.ref041","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1186\/s12889-020-10033-8","article-title":"Intersection of HIV and Anemia in women of reproductive age: a 10-year analysis of three Zimbabwe demographic health surveys, 2005\u20132015","volume":"21","author":"PN Gona","year":"2021","journal-title":"BMC Public Health"},{"issue":"11","key":"pone.0293084.ref042","doi-asserted-by":"crossref","first-page":"2051s","DOI":"10.3945\/jn.110.123463","article-title":"Women in resource-poor settings are at risk of inadequate intakes of multiple micronutrients","volume":"140","author":"LE Torheim","year":"2010","journal-title":"The Journal of nutrition"},{"issue":"2","key":"pone.0293084.ref043","doi-asserted-by":"crossref","first-page":"e0218695","DOI":"10.1371\/journal.pone.0218695","article-title":"Severe anaemia complicating HIV in Malawi; Multiple co-existing aetiologies are associated with high mortality.","volume":"15","author":"MHW Huibers","year":"2020","journal-title":"PLoS One"},{"issue":"1","key":"pone.0293084.ref044","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1186\/s13000-020-01033-8","article-title":"Clinician-ordered peripheral blood smears have low reimbursement and variable clinical value: a three-institution study, with suggestions for operational efficiency","volume":"15","author":"AK Beckman","year":"2020","journal-title":"Diagnostic pathology"},{"key":"pone.0293084.ref045","author":"AV Hoffbrand","year":"2015","journal-title":"Essential Haematology. 7th ed. John Wiley"},{"key":"pone.0293084.ref046","author":"DJ Weatherall","year":"2001","edition":"4"},{"key":"pone.0293084.ref047","volume-title":"Hematology: Basic Principles and Practice","author":"R Hoffman","year":"2018","edition":"7"},{"key":"pone.0293084.ref048","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1111\/ijlh.12082","article-title":"Red blood cell morphology","volume":"35","author":"J. 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