The historical background, epidemiology and changing pattern of clinical disease as seen in Malaysia is reviewed. The preliminary results of the longitudinal study of epidemiology of dengue in Malaysia is also presented. Studies led by Rudnick et al. over some 18 years have established that the disease is endemically transmitted by both Aedes aegypti and Aedes albopictus causing illnesses ranging from mild febrile episodes through classical dengue fever, dengue haemorrhagic fever and the dengue shock syndrome. The first epidemic occurred in 1962 in Penang, and the second major epidemic in 1974 in Selangor. From then on epidemics seem to occur every 4 years, i.e. 1978, and then in 1982. With increasing number of cases being seen from the end of 1985 and in 1986, and with the increasing numbers of positive virus isolates, another epidemic may occur this year. Though in the early years, mainly children were affected, recently more cases are being seen in 16-30 years age group. There is also a changing pattern in the clinical presentation of the cases. The clinician has to be aware of the various modes of presentation of this sinister disease. A high index of suspicion is needed for early diagnosis, as management is mainly symptomatic and there is no specific drug as yet to combat the shock and bleeding manifestations.
Dengue represents a substantial burden in many tropical and sub-tropical regions of the world. We estimated the economic burden of dengue illness in Malaysia. Information about economic burden is needed for setting health policy priorities, but accurate estimation is difficult because of incomplete data. We overcame this limitation by merging multiple data sources to refine our estimates, including an extensive literature review, discussion with experts, review of data from health and surveillance systems, and implementation of a Delphi process. Because Malaysia has a passive surveillance system, the number of dengue cases is under-reported. Using an adjusted estimate of total dengue cases, we estimated an economic burden of dengue illness of US$56 million (Malaysian Ringgit MYR196 million) per year, which is approximately US$2.03 (Malaysian Ringgit 7.14) per capita. The overall economic burden of dengue would be even higher if we included costs associated with dengue prevention and control, dengue surveillance, and long-term sequelae of dengue.
We described and quantified epidemiologic trends in dengue disease burden in 5 Asian countries (Indonesia, Thailand, Malaysia, Philippines, and Vietnam) and identified and estimated outbreaks impact over the last 3 decades. Dengue surveillance data from 1980 to 2010 were retrieved from DengueNet and from World Health Organization sources. Trends in incidence, mortality, and case fatality rate (CFR) were systematically analyzed using annual average percent change (AAPC), and the contribution of epidemic years identified over the observation period was quantified. Over the 30-year period, incidence increased in all countries (AAPC 1980-2010: 6.7% in Thailand, 10.4% in Vietnam, 12.0% in Indonesia, 18.1% in Malaysia, 24.4% in Philippines). Mortality also increased in Indonesia, Malaysia, and Philippines (AAPC: 6.8%, 7.0%, and 29.2%, respectively), but slightly decreased in Thailand and Vietnam (AAPC: -1.3% and -2.5%), and CFR decreased in all countries (AAPC: -4.2% to -8.3%). Epidemic years, despite representing less than a third of the observation period, contributed from 1 to 3 times more cases versus nonepidemic years. Implementation of more sensitive surveillance methods over the study period may have contributed to a reporting or ascertainment bias in some countries. Nonetheless, these data support the urgent need for novel, integrated, or otherwise effective dengue prevention and control tools and approaches.
During an outbreak of chikungunya in a dengue hyperendemic area within the Kinta district of Perak, two patients with acute febrile illness were laboratory confirmed to have co-infection of both dengue and chikungunya viruses in their blood. The concomitant presence of two types of viruses transmitted by the same vector in a susceptible population contributed to the resultant event. A good understanding of virus vector ecology in association with population dynamics and wider application of improved laboratory techniques by using different cell-lines suited for optimal replication of each type of virus and the correct utilization of powerful molecular techniques will enhance accurate diagnosis of these infectious diseases.
We report a newborn baby girl with acute dengue due to vertical transmission. A 31 year old factory worker of 38+ week gestation, gravida 5 para 3+1, developed acute dengue fever two days prior to delivery. She delivered a normal term baby girl by spontaneous vaginal delivery and recovered uneventfully without peripartum haemorrhage despite the presence of thrombocytopenia. The baby girl developed low grade fever on day four of post-natal life and except for the transient thrombocytopenia, also recovered uneventfully following three days of mild illness. The clinical diagnosis of acute dengue virus infection was confirmed by laboratory tests.
A previously well 13-year-old boy presented with a short history of fever and altered mental status. His mother was admitted for dengue fever and there had been a recent dengue outbreak in their neighbourhood. He was diagnosed with dengue encephalitis as both his dengue non-structural protein 1 (NS-1) antigen and cerebrospinal fluid (CSF) dengue polymerase chain reaction (PCR) were positive. He did not have haemoconcentration, thrombocytopenia or any warning signs associated with severe dengue. He recovered fully with supportive treatment. This case highlights the importance of considering the diagnosis of dengue encephalitis in patients from dengue endemic areas presenting with an acute febrile illness and neurological symptoms.
The aims of this study were to determine the seroprevalence of acute dengue in Universiti Kebangsaan Malaysia (UKM) Medical Centre and its correlation with selected haematological and biochemical parameters.
Dengue vaccine development has been one of the strategies to reduce dengue incidence in the world alongside with other horizontal interventions such as vector control and the transgenic mosquito programmes. The objective of this paper is to evaluate the safety, reactogenicity and immunogenicity of dengue vaccine clinical trials for the last ten years systematically through a descriptive review. This paper discusses safety issues like adverse events, systemic adverse reactions, injection site reactions, viraemia, morbidity and mortality as well as immunogenicity which measures effectiveness through mean geometric titre and seropositive rates. Adverse events were seen to range from 0% to 28.3%. Immunogenicity was noted to increase post 1st and 2nd dose and decrease post 3rd dose. The seropositivity at baseline ranged between 53.1% and 97.8% at post 3rd dose, and it was 88.5% for at least four serotypes. The dengue vaccine studies that were reviewed were shown to be relatively safe with low reactogenicity, however the immunogenicity was unequal and waning. The immunogenicity waned post 3rd dose showing a decrease in all serotypes of varying degrees although the seropositivity, on average, at post 3rd dose was 97.8%. It can be concluded that dengue vaccine development would require further studies on its unequal and waning immunogenicity, which could result in a more severe form of dengue following wild infection, during re-immunisation, especially if there is variation in the circulating virus.
We present a rare case of a patient diagnosed with probable dengue fever sustaining an intracranial haemorrhage after a trivial motor vehicle accident. From the literature reviewed, it was noted that there have been no reports of dengue fever presenting with an intracranial haemorrhage, and the association is more common in patients diagnosed with dengue hemorrhagic fever and/or dengue shock syndrome.
Matched MeSH terms: Dengue/complications*; Severe Dengue/complications
A consecutive series of 24 patients with clinical features of primary dengue infection and 22 controls (14 patients with viral fever of unknown origin and 8 healthy subjects) were assayed for serum levels of tumour necrosis factor (TNF). The acute sera of the 24 patients with clinical dengue infection were positive for dengue virus-specific IgM antibody. Clinically, 8 had dengue fever (DF), 14 dengue haemorrhagic fever (DHF) and 2 dengue shock syndrome (DSS). All 16 patients with DHF/DSS had significantly elevated serum TNF levels but the 8 DF patients had TNF levels equivalent to that in the 22 controls. A case is made for augmented TNF production having a role for the pathophysiological changes observed in DHF/DSS and mediator modulation as a possible therapeutic approach to treatment.
Dengue fever, Dengue hemorrhagic fever and Dengue shock syndrome within the dengue complex is a sinister disease of great public health importance and continues to ravage children, young adults and the aged in Malaysia. The history of the disease is traced for over the years and the changing pattern of clinical presentation are noted. Various hospital based studies have been compared and the pathognomonic features of the disease in Malaysia are highlighted.
The transmission of dengue virus (DENV) from an infected Aedes mosquito to a human, causes illness ranging from mild dengue fever to fatal dengue shock syndrome. The similar conserved structure and sequence among distinct DENV serotypes or different flaviviruses has resulted in the occurrence of cross reaction followed by antibody-dependent enhancement (ADE). Thus far, the vaccine which can provide effective protection against infection by different DENV serotypes remains the biggest hurdle to overcome. Therefore, deep investigation is crucial for the potent and effective therapeutic drugs development. In addition, the cross-reactivity of flaviviruses that leads to false diagnosis in clinical settings could result to delay proper intervention management. Thus, the accurate diagnostic with high specificity and sensitivity is highly required to provide prompt diagnosis in respect to render early treatment for DENV infected individuals. In this review, the recent development of neutralizing antibodies, antiviral agents, and vaccine candidates in therapeutic platform for DENV infection will be discussed. Moreover, the discovery of antigenic cryptic epitopes, principle of molecular mimicry, and application of single-chain or single-domain antibodies towards DENV will also be presented.