Phylogenetic and ecologic perspectives of a monkeypox outbreak, southern Sudan, 2005

Abstract

Identification of human monkeypox cases during 2005 in southern Sudan (now South Sudan) raised several questions about the natural history of monkeypox virus (MPXV) in Africa. The outbreak area, characterized by seasonally dry riverine grasslands, is not identified as environmentally suitable for MPXV transmission. We examined possible origins of this outbreak by performing phylogenetic analysis of genome sequences of MPXV isolates from the outbreak in Sudan and from differing localities. We also compared the environmental suitability of study localities for monkeypox transmission. Phylogenetically, the viruses isolated from Sudan outbreak specimens belong to a clade identified in the Congo Basin. This finding, added to the political instability of the area during the time of the outbreak, supports the hypothesis of importation by infected animals or humans entering Sudan from the Congo Basin, and person-to-person transmission of virus, rather than transmission of indigenous virus from infected animals to humans.

Figure 1

A) Phylogenetic tree produced from genome sequences (189,830 nt) of the 11 MPXV isolates. The separation between West African and Congo Basin clades is highly supported; the Sudan isolate is included within the Congo Basin clade. Posterior probabilities are indicated by the number 1 at each node. Scale bar indicates nucleotide substitutions per site. B) Map of geographic distribution of the isolates. Numbers correspond to those in Table 1; strains 1, Copenhagen 1958 and 2, Walter Reed 1961, were from laboratory samples and are not represented on the map. 3, Liberia 1970; 4, Sierra Leone 1970; 5, USA/Ghana 2003 039; 6, USA/Ghana 2003 044; 7, Impfondo 2003; 8, Mindembo 1979; 9, Nuria 2005; 10, Yandongi 1986; and 11, Sankuru 1996. Triangles indicate West African clade; circles indicate Congo Basin clade.

Figure 2

A) Predicted geographic distribution in central and western Africa of suitable environments for monkeypox virus transmission on the basis of the Maxent algorithm (www.cs.princeton.edu/~schapire/maxent/). Gray shading represents suitable environmental conditions identified by the algorithm; circles indicate localities of human monkeypox cases used to build the ecological niche models. Stars indicate localities reported during the human monkeypox outbreak in southern Sudan in 2005. B) Scatterplot using the first 3 principal components (PC1, PC2, and PC3) of the environmental variables in sub-Saharan Africa. Gray dots, environmental conditions in the entire area; black dots, suitable conditions identified by the ecological niche models; human monkeypox case localities; green squares, localities where monkeypox was reported in southern Sudan. Inset shows scatterplot scale.

Figure 3

Comparison of a right-end segment from genomes of monkeypox virus (Nuria Sudan 2005 and Yandongi DRC1986. Numbers above genome map are nucleotide positions. Gray boxes represent DNA sequence identity in the 2 genomes; black represents differences. The 2 large black boxes illustrate the insertion/deletion event found in Sudan isolates 1 and 2. A region from the left end of the genome has been inserted where a portion of the right end (shown in Yandongi) has been deleted. Thin black horizontal lines represent gaps in the alignment. Open reading frames are shown in white. Open reading frame names were assigned with reference to MPXV genomes available at the Poxvirus Bioinformatics Resource Center (www.poxvirus.org). Segment boxes with dots indicate unknown genome sequences; TNFr, tumor necrosis factor receptor; U(fr), unknown fragment; VirFHR, virulence factor host range; AnHR, ankyrin host range; IL18BP, interleukin 18 binding protein; UL, ubiquitin ligase; IL1rAnt interleukin 1 receptor antagonist; EGF, epidermal growth factor; ChBP, chemokine binding protein; NMDAr, N-methyl D-aspartate receptor-like protein.