Clinical characterization and placental pathology of mpox infection in hospitalized patients in the Democratic Republic of the Congo

Abstract

We describe the results of a prospective observational study of the clinical natural history of human monkeypox (mpox) virus (MPXV) infections at the remote L’Hopital General de Reference de 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 Mpox 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 mpox. 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 3 of 4 patients who were pregnant at admission, with the placenta of one fetus demonstrating prominent MPXV infection of the chorionic villi. 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 mpox rash (99.5%) and lymphadenopathy (98.6%). The single patient without the classic mpox rash had been previously vaccinated against smallpox. 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 higher maximum geometric mean values than survivors for the following variables, respectively: viral DNA in blood (DNAemia); maximum lesion count; day of admission mean AST and ALT.

Mpox (Monkeypox) in Pregnancy: Viral Clade Differences and Their Associations with Varying Obstetrical and Fetal Outcomes

“…Although this figure was generated from a single study in DR Congo, the four pregnant women in that investigation were not pre-selected and, with the exception of concomitant malaria in one woman, had no significant obstetrical co-morbidities. Their pregnancies culminated in two miscarriages, one stillborn fetus with confirmed infection and Congenital Mpox Syndrome, and one live birth [ 31 , 32 , 34 ]. This should not be surprising, as mpox Clade I has the highest case fatality rate of all mpox clades among non-pregnant individuals, between 10 and 15%.…”

“…In order to investigate the natural history of mpox in an endemic region, the Kole Human Monkeypox Infection Study was performed in the Sankuru Province of DR Congo from March 2007 to July 2011 [ 31 , 32 ]. A cohort of 222 symptomatic patients, of whom 36% were female, were enrolled at the General Hospital of Kole located in a remote town in a region of tropical rainforest where mpox is endemic.…”

“…She had confirmed mpox viremia that rapidly increased from 102 to 106 copies/mL with cessation of fetal movement. Twenty-one days after the onset of fever, a stillborn fetus was delivered at 21 weeks gestation [ 31 , 32 , 33 ]. A specimen taken for PCR at the time of membrane rupture by transcutaneous amniocentesis was positive for mpox virus at the level of 2.6 × 10 7 genome copies/mL.…”

Early administration of tecovirimat shortens the time to mpox clearance in a model of human infection

“…Bridging data from NHPs to humans is contingent upon several hypotheses. First, the experimental model of mpox infection in NHPs is more severe than in humans, with an extensive and prolonged viremia in all animals, compared to the transient and low-level viremia generally observed in humans [ 4 , 6 , 7 ]. Additionally, the NHP model suggested that mpox infection could modify tecovirimat PK, requiring drug exposure analysis in clinical studies [ 10 , 14 ].…”

“…However, in the 2022 outbreak, mpox has been predominantly reported among men who have sex with men [ 1 ]. Little data are available on the natural history of mpox infection, and findings rely on scarce samplings from small cohorts [ 4 – 6 ]. In a study conducted in Spain, 77 individuals were enrolled shortly after symptom onset and followed until viral clearance [ 7 ].…”