Kaur et al. Journal of Physiological Anthropology (2020) 39:19 https://doi.org/10.1186/s40101-020-00230-0 ORIGINAL ARTICLE Open Access The east coast districts are the possible epicenter of severe dengue in Sabah Narinderjeet Kaur1, Syed Sharizman Syed Abdul Rahim1, Joel Judson Jaimin2, Jiloris Julian Frederick Dony2, Koay Teng Khoon3 and Kamruddin Ahmed4,5* Abstract Background: Malaysia recorded the highest number of dengue cases between 2014 and 2017. There are 13 states and three federal territories in Malaysia, and each area varies in their prevalence of dengue. Sabah is one of the states situated in Borneo, Malaysia. Although dengue has been increasing for the last several years, no study was being done to understand the burden and serotype distribution of the dengue virus (DENV) in Sabah. Therefore, the present study was carried out to understand the epidemiology of the dengue infection and the factors responsible for severe dengue in Sabah. Methods: Data on dengue infection were extracted from the dengue database of the state of Sabah from 2013 through 2018. DENV NS-1-positive serum samples from multiple sites throughout Sabah were sent to the state public health laboratory, Kota Kinabalu Public Health Laboratory, for serotype determination. The analysis of factors associated with severe dengue was determined from the data of 2018 only. Results: In 2013, there were 724 dengue cases; however, from 2014, dengue cases increased exponentially and resulted in 3423 cases in 2018. Increasing dengue cases also led to increased dengue mortality. The number of dengue deaths in 2013 was only five which then gradually increased, and in 2018, 29 patients died. This is an increase of 580% from 2013 to 2018. Deaths were considerably more in the districts of the east coast of Sabah compared with districts in the west coast. During the study period, all DENV serotypes could be identified as serotypes circulating in Sabah. In 2018, the predominant serotype was DENV-3. The monthly peak of dengue infection varied in different years. In the logistic regression analysis, it was identified that children were 6.5 times, patients infected with mixed serotype of DENV were 13 times, and cases from the districts of the east coast were 5.2 times more likely to develop severe dengue. Conclusions: An increasing trend of dengue infection has been observed in Sabah. The burden of dengue, severe dengue, and mortality was noted especially in the districts of the east coast of Sabah. Severe dengue was most likely developed in children, cases from the east coast, and patients infected with mixed serotype of DENV. Keywords: Dengue, Severe dengue, Sabah, Serotype, Genotype * Correspondence: [email protected] 4Borneo Medical and Health Research Centre, Faculty of Medicine and Health Sciences, Universiti Malaysia Sabah, 88400 Kota Kinabalu, Sabah, Malaysia 5Department of Pathobiology and Medical Diagnostics, Faculty of Medicine and Health Sciences, Universiti Malaysia Sabah, Jalan UMS, 88400 Kota Kinabalu, Sabah, Malaysia Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Kaur et al. Journal of Physiological Anthropology (2020) 39:19 Page 2 of 11 Background cause of this increase is not known, this might be due to Dengue fever is a viral infection that is transmitted to improved notification rates as well as access to better diag- humans by the bite of infected Aedes mosquitoes. Glo- nostic tools. However, the possible reasons for the in- bally, every year, an estimated 390 million people are in- crease in mortality remain obscure leading us to wonder fected with dengue [1]. About 75% of these occur in whether the variation in serotype is the contributing factor Southeast Asia and Western Pacific regions [2]. Before to the increasing cases and mortality [14]. 1970, only nine countries were endemic for dengue; A similar pattern of increasing trend of dengue infection however, now, 120 countries are affected indicating den- is also observed in Sabah which needs immediate mea- gue is spreading at an alarming pace [3]. It is thought sures to assess this regional issue. However, data on the that global warming might have increased the survival serotype distribution in Sabah is still lacking [15]. This re- and/or migration of mosquitoes into previously non- quires a comprehensive study on the epidemiology and endemic areas outside the tropics. Globalization, circulating serotypes in Sabah to determine whether they urbanization, trade, and travels [4] might have also con- are associated with increased virulence or whether other tributed to the spread of dengue. associated factors are responsible. The aim of this study is Dengue infection is generally mild [5], but in 5 to 20% to determine the burden of dengue as well as to identify of cases, it may progress to severe dengue depending on the circulating serotypes of DENV in Sabah during the the immunity of the person [4, 5]. Severe dengue is man- past 6 years along with the temporal patterns and other ifested by plasma leakage, hemorrhage and organ dys- factors that are associated with severe dengue. The infor- function, and even death [6]. Early supportive care can mation obtained from this study will be useful to formu- reduce mortality in severe dengue cases; however, there late a policy for dengue control in this state. is no reliable method to predict progression to severe dengue. The warning signs for severe dengue have a low Methods positive predictive value and develop only later in the Study area disease where it might already be too late [5]. The study was performed in Sabah, Malaysia, situated in Dengue virus (DENV) is a positive-sense, single-stranded thenorthernpartofBorneoisland.Thesizeofthestateis RNA virus found in the genus Flaviviridae. It is classified 73,904 km2 with a population of 3.9 million [16]. Sabah has into four main serotypes (DENV-1, DENV-2, DENV-3, and land borders with the Malaysian state of Sarawak to the DENV-4), which are distinct genetically but cause similar southwest and Indonesia’s Kalimantan region to the south. disease features. Infection withoneoftheserotypesisbe- It also shares maritime borders with Vietnam to the west lieved to produce durable, life-long, homotypic immunity and the Philippines to the north and east. Sabah has abun- against the particular serotype; however, it only generates dant natural resources, and its economy is strongly export partial and transient cross-protection against the other oriented.Itsprimaryexportsincludeoil,gas,timber,and three serotypes. This allows for sequential dengue infec- palm oil. The other major industries are agriculture and tions with other serotypes in the same individual [1]. ecotourism. The capital of Sabah is Kota Kinabalu, and the Recently, the Asia Pacific region has been burdened state is divided into Kudat, Interior, Sandakan, Tawau, and with an increased threat of dengue. Thailand is experien- west coast divisions with a total of 23 districts. cing the largest dengue epidemic in more than 20 years [7]. The escalating cases have also been observed in Bangladesh [8]. In the Philippines [9], Laos [10], and Case definitions Myanmar [11], similar patterns of increased cases, sever- This paper followed WHO’s 2009 criteria for case defin- ity, and mortality were observed. A study in Sri Lanka ition of dengue fever and severe dengue [17]. Dengue is identified that the increasing number of dengue cases defined as a combination of two or more clinical findings and the changes in the virulence of the virus were due in a person with fever. The clinical findings include nau- to the shifting of genotypes and subtypes of the circulat- sea, vomiting, rash, aches and pains, a positive tourniquet ing DENVs [12]. This diversity amongst genotypes and test, leukopenia, and the following warning signs: abdom- serotypes is one of the major challenges in the develop- inal pain or tenderness, persistent vomiting, clinical fluid ment of tetravalent vaccines [13]. accumulation, mucosal bleeding, lethargy, restlessness, Dengue is endemic in Malaysia, and the first case was and liver enlargement. The presence of a warning sign detected back in 1902 [6]. It is prevalent throughout the may predict severe dengue in a patient. year although peak transmission occurs in the late mon- Severe dengue is defined as dengue with symptoms of either soon season. Malaysia recorded the highest number of severe plasma leakage leading to shock or fluid accumulation dengue cases through 2014 and 2016 [6], where 2015 ob- with respiratory distress, severe bleeding or severe organ served a peak with 120,836 cases and 336 deaths, which impairment such as elevated transaminases ≥ 1000 IU/L, might translate into one death daily [6]. Although the impaired consciousness, or heart impairment. Kaur et al. Journal of Physiological Anthropology (2020) 39:19 Page 3 of 11 Data preparation package (International Business Machines Corporation, Data on dengue cases and death from 2013 through Armonk, NY, USA).