www.thelancet.com/infection Vol 24 November 2024 / 線上發布 August 28, 2024 https://doi.org/10.1016/ S1473-3099(24)00564-4

在過去的幾個月裡，許多作者報導了一種主要在剛果民主共和國流行的所謂危險的mpox分支I的爆​​發，該分支導致的症狀，比在西非流行並且在2022-23期間於全球爆發的分支II更嚴重。 然而，其中許多陳述要不是沒有得到證實，要不就是參考了邦吉 (Bunge) 及其同事等之系統性回顧。這項2022 年回顧文獻的結論是，分支I 導致的致死率 (CFR) 顯著高於分支II（分支I：10.6% [95% CI 8.4–13.3] 對應 分支II：3. 6% [1.7–6.8]）然而，邦吉及其同事比較了在重要特徵的歷史人群上存在根本的差異。於 1981 年至 1986 年間在剛果民主共和國診斷出的 338 例高致死率 (CFR) 病例的最大世代幾乎全部由中位年齡為4.4 歲的兒童組成（只有 4% > 15 歲），相較於奈及利亞的最大世代（2017-18 年診斷出的122 例）主要則由中位年齡為29 歲的年輕人組成。由於與天花類似，兒科患者的 MPOX 嚴重程度似乎比成人嚴重得多，因此年齡可能是造成 CFR 差異的原因。例如，在 20 世紀 80 年代剛果民主共和國的世代中，47 名 9 歲以上的病例中沒有一人死亡。值得注意的是，所有演化支 I 的歷史資料都可能來自演化支 Ia，而不是新偵測到的演化支 Ib。

          隨著病例數不斷增加，剛果民主共和國MPOX相關致死率近幾個月持續下降（圖）。 2024 年初，致死率接近 8%，但現在已降至 3% 左右，這顯示最初存在報告的偏差。截至2024 年8 月9 日，15 歲以下兒童佔MPOX 病例的66%，佔MPOX 死亡人數的82%。然而，在目前疫情中亦僅觀察到 I 類的中非共和國，2024 年的 258 例病例中尚未報告死亡。造成區域差異的原因有很多，例如報告或出版上的偏見、醫療保健和愛滋病毒狀況的差異。晚期愛滋病毒感染似乎是嚴重病程的主要危險因子。有關愛滋病毒盛行率的資訊目前尚不清楚，尤其是在較早的研究中，但在奈及利亞世代中，七名死亡者當中至少有四人可能與愛滋病有關。

          總之，目前無法就mpox進化枝之間是否存在任何臨床差異做出有效的陳述。儘管在一些非洲國家，MPOX 無疑是一種嚴重威脅，且病例數量不斷增加，但作者對該疾病的嚴重性或獨特傳播模式的不斷升級的陳述上應該謹慎以對。需要更可靠的流行病學數據來確定進化枝之間的潛在差異，特別是關於新檢測到的進化枝 Ib。

我聲明沒有競爭利益。

克里斯蒂安·霍夫曼 hoffmann@ich-hamburg.de

ICH研究中心，漢堡20095，德國；醫學二系，石勒蘇益格-荷爾斯泰因大學醫院，基爾校區，基爾，德國

Mpox—is there a more dangerous new clade?

www.thelancet.com/infection Vol 24 November 2024 / Published Online August 28, 2024 https://doi.org/10.1016/ S1473-3099(24)00564-4

In the past few months, many authors have reported on an outbreak of a so-called dangerous clade I of mpox circulating mainly in DR Congo, which causes more severe symptoms than clade II that has been prevalent in west Africa, and during the global outbreak in 2022–23. However, many of these statements are either not substantiated or refer to systematic reviews such as Bunge and colleagues. This 2022 review concluded that clade I causes a significantly higher case fatality rate (CFR) than clade II (clade I: 10·6% [95% CI 8·4–13·3] vs clade II: 3·6% [1·7–6·8]). However, Bunge and colleagues compared historical populations that differed fundamentally in important characteristics. The largest cohort of 338 cases with a high CFR, who were diagnosed in DR Congo between 1981 and 1986, was comprised almost exclusively of children with median age of 4·4 years (with only 4% >15 years). By contrast, the largest cohort from Nigeria (122 cases diagnosed in 2017–18) was comprised of mostly young adults with median age of 29 years. As the severity of mpox, similar to smallpox, appears to be much greater in paediatric patients than adults, age alone might be responsible for the differences in CFRs. For example, in the DR Congo cohort from the 1980s, none of 47 cases older than nine years died. Of note, all the historical data for clade I are presumably from clade Ia, not the newly detected clade Ib.

         With increasing numbers of cases, the mpox-associated CFR in the DR Congo has been falling continuously in recent months (figure). At the beginning of 2024, the CFR was almost 8% but has now fallen to around 3%, suggesting that initially a reporting bias was present. As of Aug 9, 2024, children younger than 15 years accounted for 66% of cases and 82% of mpox deaths. However, in the Central African Republic, which also exclusively observes clade I in the current outbreak, no deaths among 258 cases have been reported in 2024. Many reasons for the regional differences are conceivable, such as differences in reporting or publication bias, medical care, and HIV status. Advanced HIV infection appears to be a major risk factor for severe courses. Information on HIV prevalence is not readily available, especially in older studies, but in the Nigerian cohort, at least four of seven deaths were probably AIDS-related.

        In summary, no valid statement can currently be made as to whether there is any clinical difference between mpox clades. Although mpox is undeniably a serious threat with increasing case numbers in some African countries, authors should be cautious about use of escalating statements about the severity or distinct transmission patterns of the disease. More robust epidemiological data is needed to determine potential differences between clades, in particular also about the newly detected clade Ib.

Figure: Cumulative case numbers (including confirmed and suspected cases) and case fatality rate for mpox in DR Congo in 2024 Reported by the Ministry of Health of DR Congo. Data from the Africa Centres of Disease Control and Prevention.

I declare no competing interests.

Christian Hoffmann hoffmann@ich-hamburg.de

ICH Study Center, Hamburg 20095, Germany; Department of Medicine II, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany