Global Outbreaks and Origins of a Chikungunya Virus Variant Carrying Mutations Which May Increase Fitness for Aedes aegypti: Revelations from the 2016 Mandera, Kenya Outbreak

Abstract

. In 2016, a chikungunya virus (CHIKV) outbreak was reported in Mandera, Kenya. This was the first major CHIKV outbreak in the country since the global reemergence of this virus in Kenya in 2004. We collected samples and sequenced viral genomes from this outbreak. All Kenyan genomes contained two mutations, E1:K211E and E2:V264A, recently reported to have an association with increased infectivity, dissemination, and transmission in the Aedes aegypti vector. Phylogeographic inference of temporal and spatial virus relationships showed that this variant emerged within the East, Central, and South African lineage between 2005 and 2008, most probably in India. It was also in India where the first large outbreak caused by this virus appeared, in New Delhi, 2010. More importantly, our results also showed that this variant is no longer contained to India. We found it present in several major outbreaks, including the 2016 outbreaks in Pakistan and Kenya, and the 2017 outbreak in Bangladesh. Thus, this variant may have a capability of driving large CHIKV outbreaks in different regions of the world. Our results point to the importance of continued genomic-based surveillance and prompt urgent vector competence studies to assess the level of vector susceptibility and virus transmission, and the impact this might have on this variant’s epidemic potential and global spread.

Mosquitoes of Etiological Concern in Kenya and Possible Control Strategies

“…have occurred over several decades in Kenya of which some have shown a tendency to recur in the same or new populations. For example, dengue fever in 1982 (Malindi, coastal region) [51], 2011 (Mandera, north-eastern) [52], and 2013–2014, 2017 (coastal region counties) [12,53]; Rift Valley fever in 1997–1998 (Garissa, north-eastern) [10], 2006–2007 (Garissa and Baringo) [11], 2014–2015, 2018 (north-eastern) [54]; yellow fever in 1992–1993 (Kerio Valley, Rift Valley region) [41]; chikungunya in 2004 (Lamu, coastal region) [55], 2016 (Mandera, north-eastern) [56], and 2018 (Mombasa, coastal region) [13].…”

Emergence of a novel chikungunya virus strain bearing the E1:V80A substitution, out of the Mombasa, Kenya 2017-2018 outbreak

“…aegypti adaptation [16], was observed. The E:1 K211E and E2:V264A double mutation was also observed in the 2016 Kenyan outbreak strain [4]. Whereas previous studies have shown strong positive selection for residues in the CHIKV E protein [4,16], none seems to have been selected for the present study.…”

“…The E:1 K211E and E2:V264A double mutation was also observed in the 2016 Kenyan outbreak strain [4]. Whereas previous studies have shown strong positive selection for residues in the CHIKV E protein [4,16], none seems to have been selected for the present study. On the contrary, the present study shows significant positive selection of position 171 in the NSP1 protein involved in virus replication (Table 2) pointing to potential evolution towards efficiency in viral replication.…”

“…From mid-December 2017 to mid-May 2018, an outbreak of chikungunya fever occurred in the coastal county of Mombasa [3]. The Mombasa outbreak followed an earlier outbreak of chikungunya in Mandera county on the Kenyan border with Somalia in 2016 [4]. The Mandera outbreak occurred 12 years after the coastal Kenya outbreak which began in Mombasa city and Lamu Island concurrently [5].…”

A Department of Defense Laboratory Consortium Approach to Next Generation Sequencing and Bioinformatics Training for Infectious Disease Surveillance in Kenya

“…Utilizing a global network of partner DoD medical research and public health laboratories, GEIS funds surveillance activities in over 70 countries to inform force health protection through timely and actionable infectious disease surveillance information (Chakhunashvili et al, 2017;Chang et al, 2018;Coleman et al, 2018;Koka et al, 2018;Anyamba et al, 2019;Guerra et al, 2019;Juma et al, 2019;Rivers et al, 2019;Rocha et al, 2019;Sugiharto et al, 2019). Unsurprisingly, development of NGS and bioinformatics methods for infectious disease surveillance and control has enabled a rapid expansion of GEIS partner studies that utilize pathogen genomic information (Frey et al, 2016;Maljkovic Berry et al, 2016, 2019aLee et al, 2017;Mullins et al, 2017;Salje et al, 2017;Cowell et al, 2018;LaBreck et al, 2018;Srijan et al, 2018;Grubaugh et al, 2019;Kim et al, 2019;Mbala-Kingebeni et al, 2019;Millar et al, 2019;Pollett et al, 2019;Wiley et al, 2019). However, NGS and bioinformatics can generally be technically challenging, as it requires specific knowledge of complex wet lab and bioinformatics processes (Maljkovic Berry et al, 2019b).…”