Exportation of Monkeypox Virus From the African Continent

Abstract

Background: The largest West African monkeypox outbreak began September 2017, in Nigeria. Four individuals traveling from Nigeria to the United Kingdom (n = 2), Israel (n = 1), and Singapore (n = 1) became the first human monkeypox cases exported from Africa, and a related nosocomial transmission event in the United Kingdom became the first confirmed human-to-human monkeypox transmission event outside of Africa.

Methods: Epidemiological and molecular data for exported and Nigerian cases were analyzed jointly to better understand the exportations in the temporal and geographic context of the outbreak.

Results: Isolates from all travelers and a Bayelsa case shared a most recent common ancestor and traveled to Bayelsa, Delta, or Rivers states. Genetic variation for this cluster was lower than would be expected from a random sampling of genomes from this outbreak, but data did not support direct links between travelers.

Conclusions: Monophyly of exportation cases and the Bayelsa sample, along with the intermediate levels of genetic variation, suggest a small pool of related isolates is the likely source for the exported infections. This may be the result of the level of genetic variation present in monkeypox isolates circulating within the contiguous region of Bayelsa, Delta, and Rivers states, or another more restricted, yet unidentified source pool.

Keywords: border health; exportation; haplotype networks; monkeypox virus; travel epidemiology; viral genomes.

Figure 1.

Timeline figure of Monkeypox virus cases exported from Nigeria in fall (August–October) of 2018 and spring (April–June) of 2019, shown above and below the timeline, respectively. Delineations between exposure time frame and incubation timeline are gradated, as variations are known to occur. Dates of travel between states are not known for UK2. Vertical black lines within the timeline for UK1 and SING indicate travel between states and/or the Federal Capital Territory. Symptom onset is based on cases reporting presence of lesions or fever prodrome. Incubation time is documented to range typically from 6 to 12 days, with an upper bound of 16 days. These numbers were used to determine likely timelines for exposure (green), as well as timeline expected to be prior to exposure (gray). Abbreviations: FCT, Federal Capital Territory; ISR, Israel; MPXV, Monkeypox virus; SING, Singapore; UK, United Kingdom.

Figure 2.

Map of southern Nigeria, indicating states visited by cases within the exportation-related group (states of interest). Shading within the map indicate states visited by individual travelers. Green-shaded states within the inset map indicate states with confirmed monkeypox cases as of April 2019. Abbreviations: BAY, Bayelsa State; FCT, Federal Capital Territory; ISR, Israel; MPX, monkeypox; SING, Singapore; UK, United Kingdom.

Figure 3.

Bayesian inference phylogenetic cladogram. Branch lengths are not informative. Blue branches represent exported cases, red branches represent in-country outbreak cases, and gray branches indicate reference samples. *Relationships with Bayesian posterior probability values >99%. Samples from epidemiologically linked Monkeypox virus clusters (blue- and yellow-highlighted boxes) served as references for genetic variation and ability of Bayesian inference to group epidemiologically linked genomes with high statistical support. Exportation-related cases are highlighted in pink.  ⁺Sequences generated for this study. Abbreviations: BAY, Bayelsa State; DM, dormouse; FCT, Federal Capital Territory; GR, Gambian pouched rat; HU, human; ISR, Israel; PD, prairie dog; RS, rope squirrel; SING, Singapore; UK, United Kingdom; US, United States.

Figure 4.

Median-joining haplotype network depicting relationships between Monkeypox virus samples based on single-nucleotide polymorphism matrix from whole genome data. Yellow-highlighted area indicates a cluster of epidemiologically related cases from Port Harcourt prison discussed previously [12], blue-highlighted samples represent epidemiologically linked cases from the 2003 United States outbreak generated from both human and animal samples, and pink-highlighted samples indicate the exportation-related cases, including the closest identified relative within Nigeria. Abbreviations: BAY, Bayelsa State; DM, dormouse; FCT, Federal Capital Territory; GR, Gambian pouched rat; Hu, human; ISR, Israel; PD, prairie dog; RS, rope squirrel; SING, Singapore; UK, United Kingdom; US, United States.