{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T15:37:02Z","timestamp":1762184222380,"version":"build-2065373602"},"reference-count":18,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T00:00:00Z","timestamp":1761868800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["TropicalMed"],"abstract":"<jats:p>Malaria remains a considerable challenge to international health, especially in returning travelers from endemic regions where exposure risk may be downplayed. Prompt and accurate diagnosis is crucial, especially when conventional diagnostic techniques are insufficient. This case report presents a 59-year-old man who developed fever, rash, and myalgia after returning from the Amazon rainforest. Initial laboratory tests demonstrated leukopenia, thrombocytopenia, transaminitis, and hyperbilirubinemia. Despite these abnormal results and a clinically suspicious presentation, malaria smears were negative. Since the symptoms did not resolve, a Karius test\u2014a plasma-based microbial cell-free DNA sequencing assay\u2014successfully detected the presence of Plasmodium vivax, thus establishing the diagnosis. The patient needed several treatment regimens for the recurrent attacks, including chloroquine and primaquine, artemether-lumefantrine, and eventually a combination of quinine and doxycycline together with a prolonged course of primaquine. His symptoms resolved completely after the last treatment regimen, along with the normalization of the blood counts and liver function tests. This case demonstrates the limitations of smear microscopy diagnosis in P. vivax infections, highlights the role of molecular diagnostics like the Karius test, and stresses the importance of preventing relapses with adequate hypnozoite clearance. It further highlights the importance of clinician awareness and diligent follow-up in cases of travel-related Malaria, especially those with unusual presentations or recurrent symptoms.<\/jats:p>","DOI":"10.3390\/tropicalmed10110310","type":"journal-article","created":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T14:00:33Z","timestamp":1762178433000},"page":"310","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Travel-Related Malaria Diagnosis on Karius Test Despite Negative Blood Smear"],"prefix":"10.3390","volume":"10","author":[{"given":"Joseph Eugene","family":"Weigold","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases, Department of Internal Medicine, East Tennessee State University, Johnson City, TN 37614, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-1035-3780","authenticated-orcid":false,"given":"Shankar","family":"Lal","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Internal Medicine, East Tennessee State University, Johnson City, TN 37614, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dima Ahmad","family":"Youssef","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Internal Medicine, East Tennessee State University, Johnson City, TN 37614, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,31]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2023). World Malaria Report 2023, WHO. Available online: https:\/\/www.who.int\/publications\/i\/item\/9789240086173."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Centers for Disease Control and Prevention (2023). Malaria Surveillance\u2014United States, 2021. MMWR Surveill. Summ., 72, 1\u201326.","DOI":"10.15585\/mmwr.ss7209a1"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Tseroni, M., Georgitsou, M., Baka, A., Pinaka, O., Pervanidou, D., Tsironi, M., Bleta, P., Charvalakou, M., Psinaki, I., and Dionysopoulou, M. (2020). The importance of an active case detection (ACD) program for malaria in migrant populations. Int. J. Environ. Res. Public Health, 17.","DOI":"10.3390\/ijerph17114080"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1128\/CMR.15.1.66-78.2002","article-title":"Rapid diagnostic tests for malaria parasites","volume":"15","author":"Moody","year":"2002","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_5","unstructured":"Centers for Disease Control and Prevention (2025, August 02). Malaria Diagnosis (United States). CDC Guidelines for Clinicians. Updated 2022, Available online: https:\/\/www.cdc.gov\/malaria\/hcp\/clinical-guidance\/diagnosis-treatment.html."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1038\/s41564-018-0349-6","article-title":"Analytical and clinical validation of a microbial cell-free DNA sequencing test for infectious disease","volume":"4","author":"Blauwkamp","year":"2019","journal-title":"Nat. Microbiol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Frickmann, H., Weinreich, F., Loderst\u00e4dt, U., Poppert, S., Tannich, E., Bull, J., Kreikemeyer, B., and Barrantes, I. (2022). Metagenomic sequencing for the diagnosis of Plasmodium spp. with different levels of parasitemia in EDTA blood of malaria patients\u2014A proof-of-principle assessment. Int. J. Mol. 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