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. 2020 Aug 20;12(9):913.
doi: 10.3390/v12090913.

Dengue Virus Serotype 4 Is Responsible for the Outbreak of Dengue in East Java City of Jember, Indonesia

Aryati Aryati  1   2 , Billy J Wrahatnala  3 , Benediktus Yohan  4 , May Fanny  5   6 , Faradila K N Hakim  3 , Eka Putri Sunari  7 , Nelly Zuroidah  7 , Puspa Wardhani  1   2 , Marsha S Santoso  4 , Dominicus Husada  8 , Ali Rohman  9 , Siti Nadia Tarmizi  10 , Justus T O Sievers  4 , R Tedjo Sasmono  4
Affiliations

Dengue Virus Serotype 4 Is Responsible for the Outbreak of Dengue in East Java City of Jember, Indonesia

Aryati Aryati et al. Viruses. .

Abstract

Outbreaks of dengue virus (DENV) in Indonesia have been mainly caused by the DENV serotype-1; -2; or -3. The DENV-4 was the least-reported serotype in Indonesia during the last five decades. We recently conducted a molecular epidemiology study of dengue in the Jember regency, East Java province, Indonesia. Dengue is endemic in the region and outbreaks occur annually. We investigated the clinical characteristics and etiology of dengue-like febrile illness in this regency to understand the disease dynamics. A total of 191 patients with clinical symptoms similar to dengue were recruited during an 11-month study in 2019-2020. Children accounted for the majority of cases and dengue burden was estimated in 41.4% of the cases based on NS1 antigen, viral RNA, and IgG/IgM antibody detection with the majority (73.4%) being primary infections. Secondary infection was significantly associated with a higher risk of severe dengue manifestation. All four DENV serotypes were detected in Jember. Strikingly, we observed the predominance of DENV-4, followed by DENV-3, DENV-1, and DENV-2. Genotype determination using Envelope gene sequence revealed the classification into Genotype I, Cosmopolitan Genotype, Genotype I, and Genotype II for DENV-1, -2, -3, and -4, respectively. The predominance of DENV-4 in Jember may be associated with a new wave of DENV infections and spread in a non-immune population lacking a herd-immunity to this particular serotype.

Keywords: Indonesia; Java; dengue; molecular epidemiology; serotype.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Map of study sites in Jember, East Java province, Indonesia.
Figure 2
Figure 2
Dengue cases in Jember regency. (A) Annual incidence rate (IR) of dengue in Jember regency, East Java province and Indonesia national data, with additional monthly incidence for Jember regency in early 2020 (extrapolated for 12 months). (B) Distribution of patient age by groups in Jember in 2019–2020.
Figure 3
Figure 3
The samples processing flow implemented in Jember dengue study.
Figure 4
Figure 4
The Maximum Clade Credibility (MCC) phylogenetic tree of DENV-1 genotype I and IV strains generated by BEAST Bayesian inference method with TrN + G evolution model calculated using E gene sequences. The red labels indicate isolates from Jember, while blue labels indicate strains from other cities in Indonesia and green labels indicate strains from the nearby Surabaya city. The number in the node indicates the posterior probability of that particular cluster, with values higher than 0.5 shown. Time to the most recent common ancestor (tmrca) is indicated as median year (95% Highest Posterior Density (HPD)).
Figure 5
Figure 5
The Maximum Clade Credibility (MCC) phylogenetic tree of DENV-2 Cosmopolitan genotype generated by BEAST Bayesian inference method with TrN + G evolution model calculated using E gene sequences. The red labels indicate isolates from Jember while blue labels indicate strains from other cities in Indonesia and green labels indicate strains from nearby Surabaya city. The number in the node indicates the posterior probability of that particular cluster, with values higher than 0.5 shown. Time to the most recent common ancestor (tmrca) is indicated as median year (95% Highest Posterior Density (HPD)).
Figure 6
Figure 6
The Maximum Clade Credibility (MCC) phylogenetic tree of DENV-3 Genotype I generated by BEAST Bayesian inference method with a TrN + G evolution model calculated using E gene sequences. The red labels indicate isolates from Jember, while blue labels indicate strains from other cities in Indonesia and green labels indicate strains from nearby Surabaya city. The number in the node indicates the posterior probability of that particular cluster, with values higher than 0.5 shown. Arabic numbers depict further grouping into DENV lineages. Time to the most recent common ancestor (tmrca) is indicated as median year (95% Highest Posterior Density (HPD)).
Figure 7
Figure 7
The Maximum Clade Credibility (MCC) phylogenetic tree of DENV-4 Genotype II generated by BEAST Bayesian inference method with TrN + G evolution model calculated using E gene sequences. The red labels indicate isolates from Jember, while blue labels indicate strains from other cities in Indonesia and green labels indicate strains from nearby Surabaya city. The number in the node indicates the posterior probability of that particular cluster, with values higher than 0.5 shown. Arabic numbers depict further grouping into DENV lineages. Time to the most recent common ancestor (tmrca) is indicated as median year (95% Highest Posterior Density (HPD)).
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