Clinical characterization of human monkeypox infections in the Democratic Republic of the Congo

We describe the results of a prospective observational study of the clinical natural history of human monkeypox virus (MPXV) infections at the remote General Reference Hospital of Kole (Kole hospital), the rainforest of the Congo River basin of the Democratic Republic of the Congo (DRC) from March 2007 until August 2011. The research was conducted jointly by the Institute National de Recherche Biomedical (INRB) and the US Army Medical Research Institute of Infectious Diseases (USAMRIID). The Kole hospital was one of the two previous WHO Monkeypox (MPX) study sites (1981-1986). The hospital is staffed by a Spanish Order of Catholic Nuns from La Congregation Des Seours Missionnaires Du Christ Jesus including two Spanish physicians, who were members of the Order as well, were part of the WHO study on human monkeypox. Of 244 patients admitted with a clinical diagnosis of MPXV infection, 216 were positive in both the Pan-Orthopox and MPXV specific PCR. The cardinal observations of these 216 patients are summarized in this report. There were three deaths (3/216) among these hospitalized patients; fetal death occurred in 4 of 5 (80%) patients who were pregnant at admission. The most common complaints were rash (96.8%), malaise (85.2%), sore throat (78.2%), and lymphadenopathy/adenopathy (57.4%). The most common physical exam findings were MPX rash (99.5%) and lymphadenopathy (98.6%). Age group of less than 5 years had the highest lesion count. Primary household cases tended to have higher lesion counts than secondary or later same household cases. Of the 216 patients, 200 were tested for IgM & IgG antibodies (Abs) to Orthopoxviruses. All 200 patients had anti-orthopoxvirus IgG Abs; whereas 189/200 were positive for IgM. Patients with hypoalbuminemia had a high risk of severe disease. Patients with fatal disease had significantly higher maximum geometric mean values than survivors for the following variables, respectively: viral DNA in blood (DNAemia, p=0.0072); maximum lesion count (p=0.0025); day of admission mean AST and ALT (p=0.0002 and p = 0.0224, respectively, adjusted p-values). Author Summary This is a prospective observational study of Human monkeypox disease, an emerging infectious disease in parts of the continent of Africa. There are certain differential characteristics when compared to other pox diseases. This paper describes the presenting symptoms and signs of human monkeypox disease, laboratory findings and makes recommendation for the medical treatment of patients with monkeypox disease. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was funded by Defense Threat Reduction Agency (DTRA) Contract W81XWH-06-2-004. Subcontract with Henry M. Jackson Foundation (HMJF) W81XWH-06-0266 for the Advancement of Military Medicine. Award received by JM, JH and PRP. CRADA W81XWH-06-0266. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: IRB, United States Army Medical Research Institute of Infectious Diseases gave ethical approval for this work. IRB, United States Medical Research and Develoment Command gave ethical approval for this work The Centers for Disease Control & Prevention gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All relevant data are within the manuscript and its supporting Information files. Data are also available from the Office of Human Research Oversight, USAMRIID for researchers who meet the criteria for access to confidential data.