{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T12:32:27Z","timestamp":1777984347289,"version":"3.51.4"},"update-to":[{"DOI":"10.12688\/wellcomeopenres.23352.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T00:00:00Z","timestamp":1760486400000}}],"reference-count":11,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T00:00:00Z","timestamp":1760486400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["225167"],"award-info":[{"award-number":["225167"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["wellcomeopenresearch.org"],"crossmark-restriction":false},"short-container-title":["Wellcome Open Res"],"abstract":"<ns3:p>Multi drug resistant tuberculosis (MDR-TB) in children is rare and requires tremendous skill and knowledge of clinicians for early detection and treatment. This case highlights the complexities in diagnosing and treating MDR-TB in young children. An 18-month-old immunocompetent boy presented with prolonged fever, sudden onset of vision loss, vomiting, and seizures, which led to a suspicion of meningitis. Given his family history of treated pulmonary TB in the father and uncle one year ago, the initial treatment followed the Nepali national protocol for non-MDR tuberculous meningitis (TBM). However, the child's lack of response to this treatment raised concerns about MDR-TB, particularly after discovering on close questioning that the uncle, who lived with the boy\u2019s family, had actually been diagnosed with MDR-TB. The diagnosis was confirmed by molecular tests of cerebrospinal fluid (CSF) and customized treatment for MDR TB meningitis (MDR TBM) administered. The boy then slowly improved and became less irritable, afebrile, seizure-free, developed spontaneous movements of all four limbs, and was discharged after one month. Delays in suspicion, confirmation, and treatment of MDR TBM led to complications of leptomeningitis with non-communicating hydrocephalus and bilateral optic atrophy, which was confirmed by magnetic resonance imaging (MRI) scan of the brain. This case highlights the importance of taking a very thorough and proper history and considering the possibility of MDR, especially in countries like Nepal where TB in general is rampant so that timely diagnosis and treatment is possible and complications are avoided.<\/ns3:p>","DOI":"10.12688\/wellcomeopenres.23352.2","type":"journal-article","created":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T15:15:14Z","timestamp":1760541314000},"page":"669","update-policy":"https:\/\/doi.org\/10.12688\/wellcomeopenres.crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Case Report: Multi drug resistant tuberculosis in an 18-month-old boy with seizure, vomiting, and loss of vision"],"prefix":"10.12688","volume":"9","author":[{"given":"Mukund Kumar","family":"Deo","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-1543-3689","authenticated-orcid":false,"given":"Amod","family":"Rayamajhi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bimala","family":"Baniya","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan","family":"Bhattarai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sristi","family":"Upadhyay","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-9846-3671","authenticated-orcid":false,"given":"Sanjeet Kumar","family":"Shrestha","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1125-2743","authenticated-orcid":false,"given":"Buddha","family":"Basnyat","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4819-0232","authenticated-orcid":false,"given":"Ajit","family":"Rayamajhi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2560","published-online":{"date-parts":[[2025,10,15]]},"reference":[{"key":"ref-1","doi-asserted-by":"publisher","first-page":"71-77","DOI":"10.4103\/jnrp.jnrp_163_18","article-title":"Clinical spectrum of Central Nervous System tuberculosis and the efficacy of revised National Tuberculosis control program in its management.","volume":"10","author":"E Maheswari","year":"2019","journal-title":"J Neurosci Rural Pract."},{"key":"ref-2","doi-asserted-by":"publisher","first-page":"21-50","DOI":"10.1016\/B978-0-12-805351-5.00003-X","article-title":"Chapter 3 - Specific clinical infections.","author":"A Wanger","year":"2017","journal-title":"Microbiology and Molecular Diagnosis in Pathology."},{"key":"ref-3","doi-asserted-by":"publisher","first-page":"632-8","DOI":"10.1136\/thoraxjnl-2011-200018","article-title":"Factors contributing to the high prevalence of Multidrug-Resistant Tuberculosis: a study from China.","volume":"67","author":"L Liang","year":"2012","journal-title":"Thorax."},{"key":"ref-4","first-page":"13086-88","article-title":"Optic atrophy in children","author":"S Olitsky"},{"key":"ref-5","doi-asserted-by":"publisher","first-page":"27-32","DOI":"10.1016\/j.jns.2009.12.012","article-title":"Vision impairment in Tuberculous Meningitis: predictors and prognosis.","volume":"290","author":"M Sinha","year":"2010","journal-title":"J Neurol Sci."},{"key":"ref-6","first-page":"1-186","article-title":"National guideline on drug resistant TB management.","year":"2019"},{"key":"ref-7","doi-asserted-by":"publisher","first-page":"185-192","DOI":"10.2147\/IDR.S135935","article-title":"Rifampicin-resistant Mycobacterium tuberculosis among tuberculosis-presumptive cases at university of Gondar Hospital, Northwest Ethiopia.","volume":"10","author":"K Jaleta","year":"2017","journal-title":"Infect Drug Resist."},{"key":"ref-8","doi-asserted-by":"publisher","first-page":"267-280","DOI":"10.1002\/JLB.MR0318-102R","article-title":"The pathogenesis of Tuberculous Meningitis.","volume":"105","author":"A Davis","year":"2019","journal-title":"J Leukoc Biol."},{"key":"ref-9","doi-asserted-by":"publisher","first-page":"330-7","DOI":"10.1016\/j.jinf.2012.12.009","article-title":"Hydrocephalus in Tuberculous Meningitis: incidence, its predictive factors and impact on the prognosis.","volume":"66","author":"T Raut","year":"2013","journal-title":"J Infect."},{"key":"ref-10","doi-asserted-by":"publisher","DOI":"10.1136\/bcr-2012-008138","article-title":"Unusual fundus examination findings in Tuberculous Meningitis.","volume":"2013","author":"R Verma","year":"2013","journal-title":"BMJ Case Rep."},{"key":"ref-11","doi-asserted-by":"publisher","first-page":"27-34","DOI":"10.1016\/j.jns.2017.01.031","article-title":"Vision loss in Tuberculous Meningitis","volume":"375","author":"R Garg","year":"2017","journal-title":"J Neurol Sci."}],"container-title":["Wellcome Open Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/wellcomeopenresearch.org\/articles\/9-669\/v2\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/wellcomeopenresearch.org\/articles\/9-669\/v2\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/wellcomeopenresearch.org\/articles\/9-669\/v2\/iparadigms","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,26]],"date-time":"2025-12-26T06:19:08Z","timestamp":1766729948000},"score":1,"resource":{"primary":{"URL":"https:\/\/wellcomeopenresearch.org\/articles\/9-669\/v2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,15]]},"references-count":11,"URL":"https:\/\/doi.org\/10.12688\/wellcomeopenres.23352.2","relation":{"has-version":[{"id-type":"doi","id":"10.12688\/wellcomeopenres.23352.1","asserted-by":"subject"}],"has-review":[{"id-type":"doi","id":"10.21956\/wellcomeopenres.27678.r138335","asserted-by":"subject"},{"id-type":"doi","id":"10.21956\/wellcomeopenres.27678.r136368","asserted-by":"subject"},{"id-type":"doi","id":"10.21956\/wellcomeopenres.27678.r143080","asserted-by":"object"},{"id-type":"doi","id":"10.21956\/wellcomeopenres.27678.r136367","asserted-by":"object"},{"id-type":"doi","id":"10.21956\/wellcomeopenres.27678.r136368","asserted-by":"object"},{"id-type":"doi","id":"10.21956\/wellcomeopenres.27678.r138335","asserted-by":"object"}]},"ISSN":["2398-502X"],"issn-type":[{"value":"2398-502X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,15]]},"assertion":[{"value":"Indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/9-669\/v2#article-reports","order":0,"name":"referee-status","label":"Referee status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.21956\/wellcomeopenres.25739.r113191, Sachin Atre, Dr. D.Y. Patil Medical College, Hospital and Research Centre, Pune, 06 Dec 2024, version 1, 1 approved with reservations, 1 not approved","URL":"https:\/\/wellcomeopenresearch.org\/articles\/9-669\/v1#referee-response-113191","order":0,"name":"referee-response-113191","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Ajit Rayamajhi<\/b>; \n<i>Posted: 06 Oct 2025<\/i>; Thanks for sharing this detailed set of reviewer comments and your thoughtful responses. Here's a polished version of your replies with improved clarity, flow, and academic tone, while preserving your original intent:  1. Importance of History Taking and Early Suspicion of MDR-TB Response: Thank you for the comment. The case study underscores the critical role of thorough history taking, meticulous contact tracing, appropriate prophylaxis for MDR-TB contacts, and the need for wider availability of GeneXpert testing in resource-limited settings to facilitate timely diagnosis and treatment of TBM and other forms of TB in children.  2. Placement of Global Burden Data in the Introduction Response: Thank you for the suggestion. In the introduction, we have emphasized that MDR-TB\u2014resulting from resistance to key first-line drugs\u2014poses a significant challenge to TB control efforts in developing countries due to limited diagnostics, medication shortages, and mismanagement. Although rare in children, MDR-TB can lead to severe complications such as hydrocephalus and optic atrophy, reinforcing the need for early suspicion and prompt intervention. While the global burden data was initially placed in the discussion section, we have now expanded it\u2014based on the first reviewer\u2019s recommendation\u2014to better integrate it into the discussion. For example: \u201cTuberculosis continues to be a major global health problem, affecting an estimated 10 million people annually, including 1.3 million children (WHO, 2023). Nearly two-thirds of new cases are concentrated in eight countries, most of which are in South Asia. Nepal reports 350\u2013450 MDR-TB cases annually and was classified by WHO in 2023 among the top 30 countries with the highest MDR\/RR-TB burden. While treatment success for drug-susceptible TB remains high, only 71% of MDR\/RR-TB cases achieve successful outcomes.\u201d  3. Terminology: \u201cMajor Anti-TB Drugs\u201d vs. \u201cMost Potent First-Line Anti-TB Drugs\u201d Response: Thank you for the suggestion. We have revised the first sentence of the second paragraph in the introduction to: \u201cIf Mycobacterium tuberculosis becomes resistant to the most potent first-line antitubercular drugs such as rifampin and isoniazid, it can cause a disease known as multidrug-resistant tuberculosis (MDR-TB).\u201d  4. Toxicity and Side Effects of MDR-TB Treatment Response: Thank you for the suggestion. We have incorporated this point into the first line of the third paragraph of the introduction: \u201cIn children, MDR-TB is rare and requires specialized clinical expertise for early detection and effective management. Moreover, the drugs used for treatment are often toxic, with long-term and potentially permanent side effects such as hearing loss.\u201d  5. INH Prophylaxis Ineffectiveness and Recommended Regimen for MDR-TB Contacts Response: Thank you for the suggestion. We have added the following to the second paragraph of the discussion section on Page 6: \u201cThis case also highlights the ineffectiveness of isoniazid prophylaxis against MDR-TB. For contacts of MDR-TB cases, the recommended regimen includes 6 months of daily levofloxacin and 4 months of daily rifampicin.\u201d  6. Updated WHO Estimate for Pediatric TB Burden Response: Thank you for the suggestion. We have updated the figure in the first line of the discussion section on Page 6 to reflect the latest WHO data: \u201cTuberculosis continues to be a major global health problem, affecting an estimated 10 million people annually, including 1.3 million children (https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/tuberculosis).\u201d  7. GeneXpert Availability and Systemic Barriers Response: Thank you for the suggestion. We have expanded the second paragraph of the discussion section to include the following: \u201cDiagnosis of MDR-TB in children remains a significant challenge. In this case, earlier recognition of MDR-TB meningitis might have been possible with a more detailed exposure history and initial CSF GeneXpert testing. However, the test was temporarily unavailable due to a shortage of cartridges in the hospital supply chain, which was resolved only after logistical improvements. Delays in machine repair and lack of trained personnel also contribute to test unavailability. The father's history of drug-susceptible TB and prior isoniazid preventive therapy created a false sense of protection, delaying suspicion of resistant disease. Subsequent exposure history involving an uncle with MDR-TB clarified the diagnosis, underscoring the importance of detailed history taking and contact tracing. This case also reinforces the ineffectiveness of isoniazid prophylaxis against MDR-TB; instead, 6 months of daily levofloxacin and 4 months of daily rifampicin is recommended. Ultimately, limited access to GeneXpert testing and trained staff in resource-constrained settings continues to hinder timely diagnosis and treatment.\u201d  &nbsp; &nbsp;","URL":"https:\/\/wellcomeopenresearch.org\/articles\/9-669\/v2#referee-comment-6291","order":1,"name":"referee-comment-6291","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.21956\/wellcomeopenres.27678.r136368, Hussein H Twabi, Kamuzu University of Health Sciences, Blantyre, 25 Oct 2025, version 2, indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/9-669\/v2#referee-response-136368","order":2,"name":"referee-response-136368","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.21956\/wellcomeopenres.27678.r138335, Milagros Zavaleta, Research and development, BTS Consultores S.A.C., Lima , 15082, Lima, 26 Dec 2025, version 2, indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/9-669\/v2#referee-response-138335","order":3,"name":"referee-response-138335","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"This work was supported by Wellcome [225167]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":4,"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"}]}}