Summary: The coronavirus disease 2019 (Covid‐19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), is an international public health crisis with devastating effects. In particular, this pandemic has further exacerbated the burden in tropical and subtropical regions of the world, where dengue fever, caused by dengue virus (DENV), is already endemic to the population. The similar clinical manifestations shared by Covid‐19 and dengue fever have raised concerns, especially in dengue‐endemic countries with limited resources, leading to diagnostic challenges. In addition, cross‐reactivity of the immune responses in these infections is an emerging concern, as pre‐existing DENV‐antibodies might potentially affect Covid‐19 through antibody‐dependent enhancement. In this review article, we aimed to raise the issue of Covid‐19 and dengue fever misdiagnosis, not only in a clinical setting but also with regards to cross‐reactivity between SARS‐CoV‐2 and DENV antibodies. We also have discussed the potential consequences of overlapping immunological cascades between dengue and Covid‐19 on disease severity and vaccine development.

Dengue fever is currently the most important mosquito-borne viral disease in Indonesia. In South Sulawesi province, most regions report dengue cases including the capital city, Makassar. Currently, no information is available on the serotypes and genotypes of the viruses circulating in the area. To understand the dynamic of dengue disease in Makassar, we carried out dengue fever surveillance study during 2007-2010. A total of 455 patients were recruited, in which antigen and serological detection revealed the confirmed dengue cases in 43.3% of patients. Molecular detection confirmed the dengue cases in 27.7% of patients, demonstrating that dengue places a significant disease burden on the community. Serotyping revealed that dengue virus serotype 1 (DENV-1) was the most predominant serotype, followed by DENV-2, -3, and -4. To determine the molecular evolution of the viruses, we conducted whole-genome sequencing of 80 isolates. Phylogenetic analysis grouped DENV-2, -3 and -4 to the Cosmopolitan genotype, Genotype I and Genotype II, respectively. Intriguingly, each serotype paints a different picture of evolution and transmission. DENV-1 appears to be undergoing a clade replacement with Genotype IV being supplanted by Genotype I. The Cosmopolitan DENV-2 isolates were found to be regionally endemic and is frequently being exchanged between countries in the region. By contrast, DENV-3 and DENV-4 isolates were related to strains with a long history in Indonesia although the DENV-3 strains appear to have been following a distinct evolutionary path since approximately 1998. To assess whether the various DENV serotypes/genotypes possess different growth characteristics, we performed growth kinetic assays on selected viruses. We observed the relatively higher rate of replication for DENV-1 and -2 compared to DENV-3 and -4. Within the DENV-1, viruses from Genotype I grow faster than that of Genotype IV. This higher replication rate may underlie their ability to replace the circulation of Genotype IV in the community.

Dengue, an acute febrile illness caused by infection with dengue virus (DENV), is endemic in Bali, Indonesia. As one of the world's most popular tourist destinations, Bali is regularly visited by domestic and international travellers, who are prone to infection by endemic pathogens, including DENV. Currently, limited data are available on the characteristics of dengue in travellers visiting Bali. Information on the epidemiology and virological aspects of dengue in these tourists is important to gain a better understanding of the dengue disease in international travellers. We performed a prospective cross-sectional dengue study involving foreign travellers visiting Bali, Indonesia in the period of 2015-17. Patients presenting at Kasih Ibu Hospital with fever and clinical symptoms of dengue were asked to participate in the study. Clinical and laboratory assessments were performed and sera were collected for molecular analysis, which included DENV serotyping, genome sequencing and phylogenetic analysis. Among the 201 patients recruited, dengue was confirmed in 133 (66.2%) of them, based on detection of NS1 antigen and/or viral RNA. Of these, 115 (86.5%) manifested dengue fever (DF) and 18 (13.5%) dengue haemorrhagic fever (DHF). The temporal predominance of infecting DENV serotype was DENV-2 (48.7%), followed by DENV-3 (36.1%), DENV-1 (9.2%) and DENV-4 (3.4%). Phylogenetic analysis of DENV based on envelope gene sequences revealed that the source of DENVs was local endemic viruses. Our study confirms that dengue is one of the causes of fever in travellers visiting Bali. Although it is a cause of significant morbidity, the majority of patients only experienced mild DF, with only a small proportion developing DHF. We revealed that DENVs isolated were autochthonous. Accurate diagnosis, preventive measures and continuous disease surveillance will be useful for better management of dengue infection in travellers.

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. We studied dengue disease in Semarang municipality, Central Java, one of the endemic regions in Indonesia. The disease occurred in wide geographical regions which include urban, rural, coastal, and highland areas. All four dengue virus serotypes were found. The infecting serotypes were not associated with disease severities. We also determined the genotype of the circulating viruses. One of the interesting findings was the presence of an old genotype of DENV-1 which has never been reported in the last three decades, which may suggest the silent circulation of this particular genotype in Semarang. These findings offer the first information of the clinical, virological and demographical aspects of the dengue disease in Semarang, Indonesia.