Spatiotemporal dynamics and recurrence of chikungunya virus in Brazil: an epidemiological study

Abstract

Background: Chikungunya virus (CHIKV) is an Aedes mosquito-borne virus that has caused large epidemics linked to acute, chronic, and severe clinical outcomes. Currently, Brazil has the highest number of chikungunya cases in the Americas. We aimed to investigate the spatiotemporal dynamics and recurrence pattern of chikungunya in Brazil since its introduction in 2013.

Methods: In this epidemiological study, we used CHIKV genomic sequencing data, CHIKV vector information, and aggregate clinical data on chikungunya cases from Brazil. The genomic data comprised 241 Brazilian CHIKV genome sequences from GenBank (n=180) and the 2022 CHIKV outbreak in Ceará state (n=61). The vector data (Breteau index and House index) were obtained from the Brazilian Ministry of Health for all 184 municipalities in Ceará state and 116 municipalities in Tocantins state in 2022. Epidemiological data on laboratory-confirmed cases of chikungunya between 2013 and 2022 were obtained from the Brazilian Ministry of Health and Laboratory of Public Health of Ceará. We assessed the spatiotemporal dynamics of chikungunya in Brazil via time series, mapping, age-sex distribution, cumulative case-fatality, linear correlation, logistic regression, and phylogenetic analyses.

Findings: Between March 3, 2013, and June 4, 2022, 253 545 laboratory-confirmed chikungunya cases were reported in 3316 (59·5%) of 5570 municipalities, mainly distributed in seven epidemic waves from 2016 to 2022. To date, Ceará in the northeast has been the most affected state, with 77 418 cases during the two largest epidemic waves in 2016 and 2017 and the third wave in 2022. From 2016 to 2022 in Ceará, the odds of being CHIKV-positive were higher in females than in males (odds ratio 0·87, 95% CI 0·85-0·89, p<0·0001), and the cumulative case-fatality ratio was 1·3 deaths per 1000 cases. Chikungunya recurrences in the states of Ceará, Tocantins (recurrence in 2022), and Pernambuco (recurrence in 2021) were limited to municipalities with few or no previously reported cases in the previous epidemic waves. The recurrence of chikungunya in Ceará in 2022 was associated with a new East-Central-South-African lineage. Population density metrics of the main CHIKV vector in Brazil, Aedes aegypti, were not correlated spatially with locations of chikungunya recurrence in Ceará and Tocantins.

Interpretation: Spatial heterogeneity of CHIKV spread and population immunity might explain the recurrence pattern of chikungunya in Brazil. These results can be used to inform public health interventions to prevent future chikungunya epidemic waves in urban settings.

Funding: Global Virus Network, Burroughs Wellcome Fund, Wellcome Trust, US National Institutes of Health, São Paulo Research Foundation, Brazil Ministry of Education, UK Medical Research Council, Brazilian National Council for Scientific and Technological Development, and UK Royal Society.

Translation: For the Portuguese translation of the abstract see Supplementary Materials section.

Figure 1:. Spatiotemporal dynamics of chikungunya between 2013 and 2022 in Brazil

(A) Number of laboratory-confirmed chikungunya cases and incidence according to laboratory-confirmed chikungunya cases per epidemiological week in all 26 Brazilian States and the Federal District, from epidemiological week 10 of 2013 (March 3–9) to epidemiological week 22 of 2022 (May 29 to June 4). (B) Maps coloured according to the incidence of laboratory-confirmed chikungunya cases per state. The map for 2022 is limited to epidemiological weeks 1–22. AC=Acre. AL=Alagoas. AM=Amazonas. AP=Amapá. BA=Bahia. CE=Ceará. ES=Espírito Santo. DF=Distrito Federal (Federal District). GO=Goiás. MA=Maranhão. MG=Minas Gerais. MS=Mato Grosso do Sul. MT=Mato Grosso. PA=Pará. PB=Paraíba. PE=Pernambuco. PI=Piauí. PR=Paraná. RJ=Rio de Janeiro. RN=Rio Grande do Norte. RO=Rondônia. RR=Roraima. RS=Rio Grande do Sul. SC=Santa Catarina. SE=Sergipe. SP=São Paulo. TO=Tocantins.

Figure 2:. Chikungunya waves in Ceará state, Brazil

(A) Number of laboratory-confirmed chikungunya cases per month from Jan 1, 2015, to May 31, 2022. (B) Number of laboratory-confirmed chikungunya cases for the first five months of each year (2015–22); datapoints correspond to total cases per month. (C) Chikungunya incidence based on age–sex distribution of epidemic waves in 2022, 2017, and 2016.

Figure 3:. Spatiotemporal distribution of chikungunya recurrence in Ceará state, Brazil

Spatiotemporal distribution of annual chikungunya incidence based on laboratory-confirmed chikungunya cases per municipality (n=184 municipalities) in Ceará from 2015 to 2022. Chikungunya incidence in 2022 includes data up to May 31.

Figure 4:. Chikungunya-related deaths in Ceará state, Brazil

(A) Spatial distribution of laboratory-confirmed chikungunya-related deaths per municipality (n=184 municipalities) in Ceará from 2016 to 2022. (B) Number of laboratory-confirmed chikungunya-related deaths and cases per month from January, 2016 to May, 2022. (C) Pearson’s correlation between laboratory-confirmed chikungunya-related deaths per month and laboratory-confirmed chikungunya cases per month from January, 2016, to May, 2022, with key months labelled. (D) The cumulative chikungunya case fatality ratio by age and sex from January, 2016, to May, 2022.

Figure 5:. Phylogenetic analysis of the ECSA genotype of CHIKV in Brazil

(A) Maximum clade credibility tree of 241 CHIKV genomes from the ECSA genotype, including 61 new CHIKV genomes (Ceará 2022, magnified section) from Ceará state generated in this study. Tips are coloured according to the source region or state of each sample. A strict molecular clock approach was used for generating the time-rooted tree. Posterior probability scores are shown next to key well supported nodes. Dates at key nodes are the estimated date of divergence from a common ancestor, with Bayesian credible intervals. (B) Regression of sequence sampling dates against root-to-tip genetic distances in a maximum likelihood phylogeny of the CHIKV-ECSA genotype in Brazil. Sequences are coloured according to source locations. ECSA=East-Central-South-African. CHIKV=chikungunya virus.