Chikungunya virus infection in Indonesia: a systematic review and evolutionary analysis

Abstract

Background: Despite the high number of chikungunya cases in Indonesia in recent years, comprehensive epidemiological data are lacking. The systematic review was undertaken to provide data on incidence, the seroprevalence of anti-Chikungunya virus (CHIKV) IgM and IgG antibodies, mortality, the genotypes of circulating CHIKV and travel-related cases of chikungunya in the country. In addition, a phylogenetic and evolutionary analysis of Indonesian CHIKV was conducted.

Methods: A systematic review was conducted to identify eligible studies from EMBASE, MEDLINE, PubMed and Web of Science as of October 16th 2017. Studies describing the incidence, seroprevalence of IgM and IgG, mortality, genotypes and travel-associated chikungunya were systematically reviewed. The maximum likelihood phylogenetic and evolutionary rate was estimated using Randomized Axelerated Maximum Likelihood (RAxML), and the Bayesian Markov chain Monte Carlo (MCMC) method identified the Time to Most Recent Common Ancestors (TMRCA) of Indonesian CHIKV. The systematic review was registered in the PROSPERO database (CRD42017078205).

Results: Chikungunya incidence ranged between 0.16-36.2 cases per 100,000 person-year. Overall, the median seroprevalence of anti-CHIKV IgM antibodies in both outbreak and non-outbreak scenarios was 13.3% (17.7 and 7.3% for outbreak and non-outbreak events, respectively). The median seroprevalence of IgG antibodies in both outbreak and non-outbreak settings was 18.5% (range 0.0-73.1%). There were 130 Indonesian CHIKV sequences available, of which 120 (92.3%) were of the Asian genotype and 10 (7.7%) belonged to the East/Central/South African (ECSA) genotype. The ECSA genotype was first isolated in Indonesia in 2008 and was continually sampled until 2011. All ECSA viruses sampled in Indonesia appear to be closely related to viruses that caused massive outbreaks in Southeast Asia countries during the same period. Massive nationwide chikungunya outbreaks in Indonesia were reported during 2009-2010 with a total of 137,655 cases. Our spatio-temporal, phylogenetic and evolutionary data suggest that these outbreaks were likely associated with the introduction of the ECSA genotype of CHIKV to Indonesia.

Conclusions: Although no deaths have been recorded, the seroprevalence of anti-CHIKV IgM and IgG in the Indonesian population have been relatively high in recent years following re-emergence in early 2001. There is sufficient evidence to suggest that the introduction of ECSA into Indonesia was likely associated with massive chikungunya outbreaks during 2009-2010.

Keywords: Chikungunya; Chikungunya virus; ECSA genotype; Indonesia; Systematic review.

Fig. 1

Flowchart of the result of literature search according to the preferred reporting items of systematic reviews and meta-analyses (PRISMA)

Fig. 2

Trends of number of chikungunya cases and incidence rates of chikungunya case (per 100,000 person years) reported to the Ministry of Health of the Republic of Indonesia from 2001 to 2016

Fig. 3

Geographical mapping of incidence rates of Chikungunya virus infection in Indonesian provinces from 2008 to 2016 (per 100,000 persons). Annual number of chikungunya cases from each Indonesian province was extracted from the Ministry of Health of the Republic Indonesia and the map was created using ArcGIS. The colour gradation indicates the incidence rates

Fig. 4

Phylogenetic tree of 127 Indonesian Chikungunya viruses and 1589 reference sequences from GenBank. The phylogenetic tree was generated using the maximum likelihood (ML) method available in the Randomized Axelerated Maximum Likelihood (RAxML) program with General Time Reversible and gamma substitution model (GTR + Γ). The tree shows the position of ten viruses of East/Central/South African (ECSA) genotype and 120 of Asian genotype from Indonesia relative to other viruses isolated worldwide

Fig. 5

The maximum clade credibility (MCC) tree of Indonesian Chikungunya virus. The tree was generated using the Bayesian Markov chain Monte Carlo (MCMC) method as implemented in BEAST using General Time Reversible (GTR) evolution model from E1 sequences. In the analysis, 127 Indonesian chikungunya viruses and 53 representative reference sequences from GenBank were included. All Indonesian Chikungunya viruses, isolated locally (red front) or isolated in neighboring countries (blue front) are grouped into Asian and East/Central/South African (ECSA) genotype