Human Monkeypox in Sierra Leone after 44-Year Absence of Reported Cases

Reynolds, Mary G.; Wauquier, Nadia; Liu, Yu; Satheshkumar, Panayampalli S.; Kanneh, Lansana D.; Monroe, Benjamin; Maïkéré, Jacob; Saffa, Gbessay; Gonzalez, Jean‐Paul; Fair, Joseph N.; Carroll, Darin S.; Jambai, Amara; Dafae, Foday; Khan, Sheik Humarr; Moses, Lina M.

doi:10.3201/eid2505.180832

Cited by 40 publications

(53 citation statements)

References 7 publications

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“…Monkeypox data from the DRC accounted for approximately one-third of the eligible articles [ 5 , 13 , 14 , 16 – 28 ]. The remaining articles had monkeypox data from the CAR [ 29 – 35 ], United States (US) [ 36 – 41 ], Nigeria [ 5 , 42 – 44 ], Republic of the Congo [ 15 , 45 – 47 ], Sierra Leone [ 42 , 48 , 49 ], Cameroon [ 5 , 50 ], Côte d’Ivoire [ 51 , 52 ], Gabon [ 53 , 54 ], United Kingdom (UK) [ 55 , 56 ], Israel [ 57 ], Liberia [ 42 ], Singapore [ 8 ], and South Sudan [formerly Sudan] [ 58 ]. (Note: two articles [ 5 , 42 ] described data for more than one country, therefore the total number of articles per country exceeds 48.)…”

Section: Resultsmentioning

confidence: 99%

The changing epidemiology of human monkeypox—A potential threat? A systematic review

Bunge¹,

Hoet²,

et al. 2022

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Monkeypox, a zoonotic disease caused by an orthopoxvirus, results in a smallpox-like disease in humans. Since monkeypox in humans was initially diagnosed in 1970 in the Democratic Republic of the Congo (DRC), it has spread to other regions of Africa (primarily West and Central), and cases outside Africa have emerged in recent years. We conducted a systematic review of peer-reviewed and grey literature on how monkeypox epidemiology has evolved, with particular emphasis on the number of confirmed, probable, and/or possible cases, age at presentation, mortality, and geographical spread. The review is registered with PROSPERO (CRD42020208269). We identified 48 peer-reviewed articles and 18 grey literature sources for data extraction. The number of human monkeypox cases has been on the rise since the 1970s, with the most dramatic increases occurring in the DRC. The median age at presentation has increased from 4 (1970s) to 21 years (2010–2019). There was an overall case fatality rate of 8.7%, with a significant difference between clades—Central African 10.6% (95% CI: 8.4%– 13.3%) vs. West African 3.6% (95% CI: 1.7%– 6.8%). Since 2003, import- and travel-related spread outside of Africa has occasionally resulted in outbreaks. Interactions/activities with infected animals or individuals are risk behaviors associated with acquiring monkeypox. Our review shows an escalation of monkeypox cases, especially in the highly endemic DRC, a spread to other countries, and a growing median age from young children to young adults. These findings may be related to the cessation of smallpox vaccination, which provided some cross-protection against monkeypox, leading to increased human-to-human transmission. The appearance of outbreaks beyond Africa highlights the global relevance of the disease. Increased surveillance and detection of monkeypox cases are essential tools for understanding the continuously changing epidemiology of this resurging disease.

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Section: Resultsmentioning

confidence: 99%

The changing epidemiology of human monkeypox—A potential threat? A systematic review

Bunge¹,

Hoet²,

et al. 2022

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“…Animals (n = 16) were dosed with a three-dose (q48h) regimen of 20 (n = 8) or 5 (n = 8) mg/kg BCV via oral gavage, so that BCV pharmacokinetics could be determined following single and repeated doses. Blood (the maximum allowed per the IACUC protocol was ;0.5 ml) was collected at 8 time points (1,2,4,8,12,24,36, and 48 h) following the first BCV administration and at 9 time points (0, 1, 2, 4, 8, 12, 24, 36, and 48 h) following the last BCV administration via venipuncture (either the saphenous or jugular vein). To prevent dehydration and pain from the repeated blood collection, animals were given DietGel Criticare (ClearH 2 O; Portland, ME, USA) gel cup supplements, subcutaneous fluids (lactated ringers fluid), and meloxicam (4 mg/ml) every 24 h.…”

Section: Methodsmentioning

confidence: 99%

“…While smallpox has been eradicated from the human population, recent studies have demonstrated a relatively easy path to virus reconstitution through the use of synthetic biology (1). Additionally, the number of monkeypox cases within Africa is growing, as is the number of African territories reporting the disease, possibly due in part to the waning immunity following smallpox vaccine cessation (2)(3)(4)(5)(6). MPXV has also been spread outside Africa, notably during the 2003 U.S. outbreak, as well as from recent imported cases of monkeypox in Israel, the United Kingdom, and Singapore (7)(8)(9).…”

mentioning

confidence: 99%

Pharmacokinetics and Efficacy of a Potential Smallpox Therapeutic, Brincidofovir, in a Lethal Monkeypox Virus Animal Model

Hutson

Kondas

Mauldin

et al. 2021

mSphere

130

121

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Smallpox, caused by Variola virus (VARV), was eradicated in 1980; however, VARV bioterrorist threats still exist, necessitating readily available therapeutics. Current preparedness activities recognize the importance of oral antivirals and recommend therapeutics with different mechanisms of action. Monkeypox virus (MPXV) is closely related to VARV, causing a highly similar clinical human disease, and can be used as a surrogate for smallpox antiviral testing. The prairie dog MPXV model has been characterized and used to study the efficacy of antipoxvirus therapeutics, including recently approved TPOXX (tecovirimat). Brincidofovir (BCV; CMX001) has shown antiviral activity against double-stranded DNA viruses, including poxviruses. To determine the exposure of BCV following oral administration to prairie dogs, a pharmacokinetics (PK) study was performed. Analysis of BCV plasma concentrations indicated variability, conceivably due to the outbred nature of the animals. To determine BCV efficacy in the MPXV prairie dog model, groups of animals were intranasally challenged with 9 × 105 plaque-forming units (PFU; 90% lethal dose [LD90]) of MPXV on inoculation day 0 (ID0). Animals were divided into groups based on the first day of BCV treatment relative to inoculation day (ID–1, ID0, or ID1). A trend in efficacy was noted dependent upon treatment initiation (57% on ID–1, 43% on ID0, and 29% on ID1) but was lower than demonstrated in other animal models. Analysis of the PK data indicated that BCV plasma exposure (maximum concentration [Cmax]) and the time of the last quantifiable concentration (AUClast) were lower than in other animal models administered the same doses, indicating that suboptimal BCV exposure may explain the lower protective effect on survival. IMPORTANCE Preparedness activities against highly transmissible viruses with high mortality rates have been highlighted during the ongoing coronavirus disease 2019 (COVID-19) pandemic. Smallpox, caused by variola virus (VARV) infection, is highly transmissible, with an estimated 30% mortality. Through an intensive vaccination campaign, smallpox was declared eradicated in 1980, and routine smallpox vaccination of individuals ceased. Today's current population has little/no immunity against VARV. If smallpox were to reemerge, the worldwide results would be devastating. Recent FDA approval of one smallpox antiviral (tecovirimat) was a successful step in biothreat preparedness; however, orthopoxviruses can become resistant to treatment, suggesting the need for multiple therapeutics. Our paper details the efficacy of the investigational smallpox drug brincidofovir in a monkeypox virus (MPXV) animal model. Since brincidofovir has not been tested in vivo against smallpox, studies with the related virus MPXV are critical in understanding whether it would be protective in the event of a smallpox outbreak.

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“…The outbreak in the US (2003) [40] and the outbreak in Nigeria (which started in 2017) [44] cover the largest part of the West African clade cases. This latter clade was also found in Sierra Leone [48,49] and the travel-related cases in Israel [57] and Singapore [8].…”

Section: Number Of Cases By Cladementioning

confidence: 63%

“…Monkeypox data from the DRC accounted for approximately one-third of the eligible articles [5,13,14,[16][17][18][19][20][21][22][23][24][25][26][27][28]. The remaining articles had monkeypox data from the CAR [29][30][31][32][33][34][35], United States (US) [36][37][38][39][40][41], Nigeria [5,[42][43][44], Republic of the Congo [15,[45][46][47], Sierra Leone [42,48,49],…”

Section: Number Of Reports By Countrymentioning

confidence: 99%

The changing epidemiology of human monkeypox – a potential threat? A systematic review

Bunge¹,

Hoet²,

Chen

et al. 2021

Preprint

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Monkeypox, a zoonotic disease caused by an orthopoxvirus, results in a smallpox-like disease in humans. Since monkeypox in humans was initially diagnosed in 1970 in the Democratic Republic of the Congo (DRC), it has spread to other regions of Africa (primarily West and Central), and cases outside Africa have emerged in recent years. We conducted a systematic review of peer-reviewed and grey literature on how monkeypox epidemiology has evolved, with particular emphasis on the number of confirmed, probable, and/or possible cases, age at presentation, mortality, and geographical spread. The review is registered with PROSPERO (CRD42020208269). We identified 48 peer-reviewed articles and 18 grey literature sources for data extraction. The number of human monkeypox cases has been on the rise since the 1970s, with the most dramatic increases occurring in the DRC. The median age at presentation has increased from 4 (1970s) to 21 years (2010-2019). There was an overall case fatality rate of 8.7%, with a significant difference between clades - Central African 10.6% (95% CI: 8.4% - 13.3%) vs. West African 3.6% (95% CI: 1.7% - 6.8%). Since 2003, import- and travel-related spread outside of Africa has occasionally resulted in outbreaks. Interactions/activities with infected animals or individuals are risk behaviors associated with acquiring monkeypox. Our review shows an escalation of monkeypox cases, especially in the highly endemic DRC, a spread to other countries, and a growing median age from young children to young adults. These findings may be related to the cessation of smallpox vaccination, which provided some cross-protection against monkeypox, leading to increased human-to-human transmission. The appearance of outbreaks beyond Africa highlights the global relevance of the disease. Increased surveillance and detection of monkeypox cases are essential tools for understanding the continuously changing epidemiology of this resurging disease.

show abstract

Human Monkeypox in Sierra Leone after 44-Year Absence of Reported Cases

Cited by 40 publications

References 7 publications

The changing epidemiology of human monkeypox—A potential threat? A systematic review

The changing epidemiology of human monkeypox—A potential threat? A systematic review

Pharmacokinetics and Efficacy of a Potential Smallpox Therapeutic, Brincidofovir, in a Lethal Monkeypox Virus Animal Model

The changing epidemiology of human monkeypox – a potential threat? A systematic review

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