Molecular Surveillance of Dengue in Semarang, Indonesia Revealed the Circulation of an Old Genotype of Dengue Virus Serotype-1

Abstract

Dengue disease is currently a major health problem in Indonesia and affects all provinces in the country, including Semarang Municipality, Central Java province. While dengue is endemic in this region, only limited data on the disease epidemiology is available. To understand the dynamics of dengue in Semarang, we conducted clinical, virological, and demographical surveillance of dengue in Semarang and its surrounding regions in 2012. Dengue cases were detected in both urban and rural areas located in various geographical features, including the coastal and highland areas. During an eight months' study, a total of 120 febrile patients were recruited, of which 66 were serologically confirmed for dengue infection using IgG/IgM ELISA and/or NS1 tests. The cases occurred both in dry and wet seasons. Majority of patients were under 10 years old. Most patients were diagnosed as dengue hemorrhagic fever, followed by dengue shock syndrome and dengue fever. Serotyping was performed in 31 patients, and we observed the co-circulation of all four dengue virus (DENV) serotypes. When the serotypes were correlated with the severity of the disease, no direct correlation was observed. Phylogenetic analysis of DENV based on Envelope gene sequence revealed the circulation of DENV-2 Cosmopolitan genotype and DENV-3 Genotype I. A striking finding was observed for DENV-1, in which we found the co-circulation of Genotype I with an old Genotype II. The Genotype II was represented by a virus strain that has a very slow mutation rate and is very closely related to the DENV strain from Thailand, isolated in 1964 and never reported in other countries in the last three decades. Moreover, this virus was discovered in a cool highland area with an elevation of 1,001 meters above the sea level. The discovery of this old DENV strain may suggest the silent circulation of old virus strains in Indonesia.

Molecular surveillance of Dengue in Sukabumi, West Java province, Indonesia

“…Our previous survey in several cities in West Java, including Sukabumi, in 2008 revealed the circulation of DENV-3 [25]. Furthermore, our recent surveys in other cities in Indonesia such as Semarang in 2012 [26] and Surabaya in 2012 (Wardhani et al, in preparation) also detected the presence of DENV-3. Therefore, given the absence of DENV-3 in Sukabumi, our data may reflect the dynamic of DENV serotype circulation in Indonesia, where serotype predominance is changing over the time.…”

“…In general, the DENV isolates in this study possessed nucleotide substitution rates similar to previous reports (Table 2), indicating the common evolutionary rate and that they had not undergone significant genetic changes over time. The information about the DENV evolutionary rate is a useful tool in monitoring whether particular strain(s) of DENV have undergone peculiar evolution, as in the case of our recent finding of the DENV-1 strain, which has undergone a very slow evolutionary rate circulating in Semarang, Indonesia [26].…”

Phylogeny of Dengue virus type 2 isolated in the Central Highlands, Vietnam

“…This proved that genotype distribution of DENV-2 remained stable in Vietnam for long time. Asian genotype 1 is also quite common in the region and is widely circulated in India, South East Asia, Africa, the Middle East, and Australia (Fahri et al, 2013).…”

Pathogenic viruses: Molecular detection and characterization

“…Firstly, the genetic material of the viruses is extracted, isolated and purified from the specimens. Types of specimens commonly collected are those which contain the maximum amount of the target virus (Johnson, 1990), for example, whole blood and oral swabs are collected and used for detection of Ebola virus (World Health Organization (WHO), 2014); posterior-pharyngeal (throat) swabs or nasal swabs for detection of avian influenza A(H5N1) virus (World Health Organization (WHO), 2006); respiratory, stool, and rectal swab (Chan et al, 2004a), sputum , urine, serum, plasma and peripheral blood leukocytes specimens (Mahony and Richardson, 2005) for detection of SARS-CoV; serum , plasma, urine (Corman et al, 2016), whole blood, amniotic fluid, cerebrospinal fluid (CSF), organ tissues such as placenta, fetal brain, eyes (Landry and George, 2017) for detection of Zika virus; saliva, CSF, tears, skin biopsy, urine for detection of rabies virus (Fooks et al, 2009), serum for detection of Coxsackievirus (Wiyatno et al, 2016), West Nile virus , Dengue virus (Fahri et al, 2013), blood for detection of Chikungunya virus , etc.…”