{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T02:46:55Z","timestamp":1791600415976,"version":"4.3.4"},"reference-count":56,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2017,12,12]],"date-time":"2017-12-12T00:00:00Z","timestamp":1513036800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Monkeypox is a smallpox-like illness that can be accompanied by a range of significant medical complications. To date there are no standard or optimized guidelines for the clinical management of monkeypox (MPX) patients, particularly in low-resource settings. Consequently, patients can experience protracted illness and poor outcomes. Improving care necessitates developing a better understanding of the range of clinical manifestations\u2014including complications and sequelae\u2014as well as of features of illness that may be predictive of illness severity and poor outcomes. Experimental and natural infection of non-human primates with monkeypox virus can inform the approach to improving patient care, and may suggest options for pharmaceutical intervention. These studies have traditionally been performed to address the threat of smallpox bioterrorism and were designed with the intent of using MPX as a disease surrogate for smallpox. In many cases this necessitated employing high-dose, inhalational or intravenous challenge to recapitulate the severe manifestations of illness seen with smallpox. Overall, these data\u2014and data from biomedical research involving burns, superficial wounds, herpes, eczema vaccinatum, and so forth\u2014suggest that MPX patients could benefit from clinical support to mitigate the consequences of compromised skin and mucosa. This should include prevention and treatment of secondary bacterial infections (and other complications), ensuring adequate hydration and nutrition, and protecting vulnerable anatomical locations such as the eyes and genitals. A standard of care that considers these factors should be developed and assessed in different settings, using clinical metrics specific for MPX alongside consideration of antiviral therapies.<\/jats:p>","DOI":"10.3390\/v9120380","type":"journal-article","created":{"date-parts":[[2017,12,12]],"date-time":"2017-12-12T13:35:00Z","timestamp":1513085700000},"page":"380","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":209,"title":["Improving the Care and Treatment of Monkeypox Patients in Low-Resource Settings: Applying Evidence from Contemporary Biomedical and Smallpox Biodefense Research"],"prefix":"10.3390","volume":"9","author":[{"given":"Mary","family":"Reynolds","sequence":"first","affiliation":[{"name":"US Centers for Disease Control and Prevention, Poxvirus and Rabies Branch, Atlanta, GA 30329, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"McCollum","sequence":"additional","affiliation":[{"name":"US Centers for Disease Control and Prevention, Poxvirus and Rabies Branch, Atlanta, GA 30329, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatrice","family":"Nguete","sequence":"additional","affiliation":[{"name":"Kinshasa School of Public Health, Kinshasa 11850, Congo"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Shongo Lushima","sequence":"additional","affiliation":[{"name":"Ministry of Health, Kinshasa 11842, Congo"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brett","family":"Petersen","sequence":"additional","affiliation":[{"name":"US Centers for Disease Control and Prevention, Poxvirus and Rabies Branch, Atlanta, GA 30329, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2017,12,12]]},"reference":[{"key":"ref_1","first-page":"56","article-title":"Monkeypox virus in relation to the ecological features surrounding human settlements in Bumba zone, Zaire","volume":"39","author":"Khodakevich","year":"1987","journal-title":"Trop. Geogr. Med."},{"key":"ref_2","first-page":"747","article-title":"Monkeypox virus: Ecology and public health significance","volume":"66","author":"Khodakevich","year":"1988","journal-title":"Bull. World Health Organ."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"718","DOI":"10.4269\/ajtmh.15-0095","article-title":"Human Monkeypox in the Kivus, a Conflict Region of the Democratic Republic of the Congo","volume":"93","author":"McCollum","year":"2015","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"934","DOI":"10.3201\/eid1306.061540","article-title":"Endemic human monkeypox, Democratic Republic of Congo, 2001\u20132004","volume":"13","author":"Rimoin","year":"2007","journal-title":"Emerg. Infect. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"16262","DOI":"10.1073\/pnas.1005769107","article-title":"Major increase in human monkeypox incidence 30 years after smallpox vaccination campaigns cease in the Democratic Republic of Congo","volume":"107","author":"Rimoin","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.tim.2011.12.001","article-title":"Outbreaks of human monkeypox after cessation of smallpox vaccination","volume":"20","author":"Reynolds","year":"2012","journal-title":"Trends Microbiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1354","DOI":"10.1016\/S0140-6736(11)61142-2","article-title":"Maculopapular lesions in the Central African Republic","volume":"378","author":"Berthet","year":"2011","journal-title":"Lancet"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1007\/s13149-016-0516-z","article-title":"Twelve cases of monkeypox virus outbreak in Bangassou District (Central African Republic) in December 2015","volume":"109","author":"Kalthan","year":"2016","journal-title":"Bull. Soc. Pathol. Exot."},{"key":"ref_9","first-page":"311","article-title":"Monkey pox virus infection in humans in the Central African Republic","volume":"78","author":"Khodakevich","year":"1985","journal-title":"Bull. Soc. Pathol. Exot. Fil."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.virol.2005.05.030","article-title":"Virulence differences between monkeypox virus isolates from West Africa and the Congo basin","volume":"340","author":"Chen","year":"2005","journal-title":"Virology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2661","DOI":"10.1099\/vir.0.81215-0","article-title":"A tale of two clades: Monkeypox viruses","volume":"86","author":"Likos","year":"2005","journal-title":"J. Gen. Virol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1742","DOI":"10.1086\/498115","article-title":"Clinical characteristics of human monkeypox, and risk factors for severe disease","volume":"41","author":"Huhn","year":"2005","journal-title":"Clin. Infect. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1056\/NEJMoa032299","article-title":"The detection of monkeypox in humans in the Western Hemisphere","volume":"350","author":"Reed","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1093\/infdis\/156.2.293","article-title":"Human monkeypox: Clinical features of 282 patients","volume":"156","author":"Jezek","year":"1987","journal-title":"J. Infect. Dis."},{"key":"ref_15","first-page":"297","article-title":"Human monkeypox: Confusion with chickenpox","volume":"45","author":"Jezek","year":"1988","journal-title":"Acta Trop."},{"key":"ref_16","first-page":"459","article-title":"Clinico-epidemiological features of monkeypox patients with an animal or human source of infection","volume":"66","author":"Jezek","year":"1988","journal-title":"Bull. World Health Organ."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"428","DOI":"10.4269\/ajtmh.2005.73.428","article-title":"Extended Interhuman Transmission of Monkeypox in a Hospital Community in the Republic of the Congo, 2003","volume":"73","author":"Learned","year":"2005","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_18","first-page":"73","article-title":"Human monkeypox: Disease pattern, incidence and attack rates in a rural area of northern Zaire","volume":"40","author":"Jezek","year":"1988","journal-title":"Trop. Geogr. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"982","DOI":"10.4269\/ajtmh.12-0758","article-title":"Detection of human monkeypox in the Republic of the Congo following intensive community education","volume":"88","author":"Reynolds","year":"2013","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1093\/inthealth\/iht029","article-title":"Enhancing health care worker ability to detect and care for patients with monkeypox in the Democratic Republic of the Congo","volume":"5","author":"Bass","year":"2013","journal-title":"Int. Health"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1177\/0300985810378649","article-title":"Animal models of orthopoxvirus infection","volume":"47","author":"Chapman","year":"2010","journal-title":"Vet. Pathol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Nalca, A., Livingston, V.A., Garza, N.L., Zumbrun, E.E., Frick, O.M., Chapman, J.L., and Hartings, J.M. (2010). Experimental infection of cynomolgus macaques (Macaca fascicularis) with aerosolized monkeypox virus. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0012880"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1581","DOI":"10.1038\/labinvest.3780373","article-title":"The pathology of experimental aerosolized monkeypox virus infection in cynomolgus monkeys (Macaca fascicularis)","volume":"81","author":"Zaucha","year":"2001","journal-title":"Lab. Investig."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1877","DOI":"10.1007\/s00705-011-1065-1","article-title":"Infection of cynomolgus macaques with a recombinant monkeypox virus encoding green fluorescent protein","volume":"156","author":"Goff","year":"2011","journal-title":"Arch. Virol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/0035-9203(85)90333-5","article-title":"The histopathology and electron microscopy of a human monkeypox lesion","volume":"79","author":"Stagles","year":"1985","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1111\/j.0303-6987.2005.00254.x","article-title":"Monkeypox virus: Histologic, immunohistochemical and electron-microscopic findings","volume":"32","year":"2005","journal-title":"J. Cutan. Pathol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1111\/j.1365-4632.2009.03788.x","article-title":"Herpes simplex virus: A histopathologic study of the depth of herpetic wounds","volume":"48","author":"Patel","year":"2009","journal-title":"Int. J. Dermatol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1001\/jamaophthalmol.2013.264","article-title":"Clinicopathological findings in persistent corneal cowpox infection","volume":"131","author":"Graef","year":"2013","journal-title":"JAMA Ophthalmol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1086\/506937","article-title":"A Case of Facial Cellulitis and Necrotizing Lymphadenitis due to Cowpox Virus Infection","volume":"43","author":"Pahlitzsch","year":"2006","journal-title":"Clin. Infect. Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1097\/01.ASW.0000280199.58260.62","article-title":"Treatment of herpes simplex virus infection: Rationale for occlusion","volume":"20","author":"Patel","year":"2007","journal-title":"Adv. Skin Wound Care"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e35","DOI":"10.1016\/j.burns.2014.01.003","article-title":"Acute generalized pustular psoriasis, von Zumbusch type, treated in the burn unit. A review of clinical features and new therapeutics","volume":"40","author":"Varman","year":"2014","journal-title":"Burns"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.jcv.2014.12.001","article-title":"Cytokine modulation correlates with severity of monkeypox disease in humans","volume":"63","author":"Johnston","year":"2015","journal-title":"J. Clin. Virol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1111\/wrr.12169","article-title":"Orf virus IL-10 accelerates wound healing while limiting inflammation and scarring","volume":"22","author":"Wise","year":"2014","journal-title":"Wound Repair Regen."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Zevin, A.S., Xie, I.Y., Birse, K., Arnold, K., Romas, L., Westmacott, G., Novak, R.M., McCorrister, S., McKinnon, L.R., and Cohen, C.R. (2016). Microbiome Composition and Function Drives Wound-Healing Impairment in the Female Genital Tract. PLoS Pathog., 12.","DOI":"10.1371\/journal.ppat.1005889"},{"key":"ref_35","first-page":"149","article-title":"Observations on the formation of smallpox scars","volume":"54","author":"Bras","year":"1952","journal-title":"AMA Arch. Pathol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1016\/j.jaad.2003.10.672","article-title":"The scarring mechanism of smallpox","volume":"50","author":"Regan","year":"2004","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1001\/archopht.121.5.715","article-title":"The ocular complications of smallpox and smallpox immunization","volume":"121","author":"Semba","year":"2003","journal-title":"Arch. Ophthalmol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1016\/j.ajo.2003.09.013","article-title":"Ocular vaccinia following exposure to a smallpox vaccinee","volume":"137","author":"Hu","year":"2004","journal-title":"Am. J. Ophthalmol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.jaad.2006.04.017","article-title":"Analysis of cases reported as generalized vaccinia during the US military smallpox vaccination program, December 2002 to December 2004","volume":"55","author":"Lewis","year":"2006","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"699","DOI":"10.7205\/MILMED-D-10-00473","article-title":"Ocular vaccinia: A consequence of unrecognized contact transmission","volume":"176","author":"Montgomery","year":"2011","journal-title":"Mil. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1093\/infdis\/jiq103","article-title":"Evaluation of therapeutic interventions for vaccinia virus keratitis","volume":"203","author":"Altmann","year":"2011","journal-title":"J. Infect. Dis."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1086\/505880","article-title":"Clinical manifestations of human monkeypox influenced by route of infection","volume":"194","author":"Reynolds","year":"2006","journal-title":"J. Infect. Dis."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"4898","DOI":"10.1128\/JVI.02525-10","article-title":"A novel respiratory model of infection with monkeypox virus in cynomolgus macaques","volume":"85","author":"Goff","year":"2011","journal-title":"J. Virol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1902","DOI":"10.1093\/infdis\/jir663","article-title":"Evaluation of Monkeypox Disease Progression by Molecular Imaging","volume":"204","author":"Dyall","year":"2011","journal-title":"J. Infect. Dis."},{"key":"ref_45","first-page":"303","article-title":"The morbid anatomy of smallpox","volume":"4","author":"Bras","year":"1952","journal-title":"Doc. Med. Geogr. Trop."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1038\/nrmicro3231","article-title":"The co-pathogenesis of influenza viruses with bacteria in the lung","volume":"12","author":"McCullers","year":"2014","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"e86","DOI":"10.1200\/JOP.2013.000923","article-title":"Evolution of the Quality Oncology Practice Initiative supportive care quality measures portfolio and conformance at a Veterans Affairs medical center","volume":"9","author":"Nipp","year":"2013","journal-title":"J. Oncol. Pract."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3807","DOI":"10.1093\/ndt\/gfs394","article-title":"Best supportive care and therapeutic plasma exchange with or without eculizumab in Shiga-toxin-producing E. coli O104:H4 induced haemolytic-uraemic syndrome: An analysis of the German STEC-HUS registry","volume":"27","author":"Kielstein","year":"2012","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/j.antiviral.2017.01.009","article-title":"Short-term clinical safety profile of brincidofovir: A favorable benefit-risk proposition in the treatment of smallpox","volume":"143","author":"Chittick","year":"2017","journal-title":"Antivir. Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2560","DOI":"10.1128\/AAC.01689-09","article-title":"Safety and Pharmacokinetics of the Anti-Orthopoxvirus Compound ST-246(R) following Repeat Oral Dosing in Healthy Adult Subjects","volume":"54","author":"Jordan","year":"2010","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2409","DOI":"10.3390\/v2112409","article-title":"Development of ST-246(R) for Treatment of Poxvirus Infections","volume":"2","author":"Jordan","year":"2010","journal-title":"Viruses"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1814","DOI":"10.1016\/S0140-6736(10)60483-7","article-title":"Tuberculosis control and elimination 2010\u201350: Cure, care, and social development","volume":"375","author":"Lonnroth","year":"2010","journal-title":"Lancet"},{"key":"ref_53","unstructured":"World Health Organization (2000). Leprosy Elimination Monitoring (LEM); Guidelines for Monitors, World Health Organization. Report No. WHO\/CDS\/CPE\/2000.17."},{"key":"ref_54","unstructured":"Kasolo, F., and Raungou, J. (2010). Technical Guidelines for Integrated Disease Surveillance and Response in the African Region."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Mucker, E.M., Chapman, J., Huzella, L.M., Huggins, J.W., Shamblin, J., Robinson, C.G., and Hensley, L.E. (2015). Susceptibility of Marmosets (Callithrix jacchus) to Monkeypox Virus: A Low Dose Prospective Model for Monkeypox and Smallpox Disease. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0131742"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"4335","DOI":"10.1128\/JVI.03029-14","article-title":"Sequence of pathogenic events in cynomolgus macaques infected with aerosolized monkeypox virus","volume":"89","author":"Tree","year":"2015","journal-title":"J. Virol."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/9\/12\/380\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T18:53:38Z","timestamp":1760208818000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/9\/12\/380"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,12,12]]},"references-count":56,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2017,12]]}},"alternative-id":["v9120380"],"URL":"https:\/\/doi.org\/10.3390\/v9120380","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,12,12]]}}}