JB, EI and ML are employees of Sanofi Pasteur. AHMZ has no conflicts of interest to declare. This does not alter our adherence to all PLOS policies on sharing data and materials.
Conceived and designed the experiments: AHMZ JB EI ML. Performed the experiments: AHMZ JB EI ML. Analyzed the data: AHMZ JB EI ML. Contributed reagents/materials/analysis tools: AHMZ JB EI ML. Wrote the paper: AHMZ JB EI ML.
A literature survey and analysis was conducted to describe the epidemiology of dengue disease in Malaysia between 2000 and 2012. Published literature was searched for epidemiological studies of dengue disease, using specific search strategies for each electronic database; 237 relevant data sources were identified, 28 of which fulfilled the inclusion criteria. The epidemiology of dengue disease in Malaysia was characterized by a non-linear increase in the number of reported cases from 7,103 in 2000 to 46,171 in 2010, and a shift in the age range predominance from children toward adults. The overall increase in dengue disease was accompanied by a rise in the number, but not the proportion, of severe cases. The dominant circulating dengue virus serotypes changed continually over the decade and differed between states. Several gaps in epidemiological knowledge were identified; in particular, studies of regional differences, age-stratified seroprevalence, and hospital admissions.
PROSPERO #
Dengue disease is a tropical and subtropical mosquito-borne viral illness, and is a major health concern in Malaysia. We conducted this literature analysis and review to describe the epidemiology of dengue disease in Malaysia between 2000 and 2012, to determine the impact of dengue disease on the Malaysian population, and to identify future research priorities. We used well-defined methods to search and identify relevant research, and data were selected according to predetermined inclusion criteria. This long-term review highlights the changing epidemiology of dengue fever in Malaysia. Although the overall incidence has stabilized in recent years, dengue disease remains a public health burden. Our review demonstrates an increased incidence of all forms of dengue disease and a predominantly adult age distribution. Changes in circulating dengue virus serotypes may have implications for the incidence and severity of dengue disease. Increasing levels of rainfall, humidity, temperature, and urbanization have been identified as risk factors for dengue disease outbreak. We believe that the recent improvements to the surveillance system in Malaysia should, if pursued over the next few years, greatly improve our understanding of the burden of dengue fever and enable us to monitor the impact of disease control measures in the future.
Dengue disease, a tropical and subtropical mosquito-borne viral illness, is a major health concern worldwide. A recent disease distribution model estimated that there were 96 million apparent dengue virus (DENV) infections globally in 2010 and that Asian countries, with 67 million apparent infections, bore a disproportionate infectious burden (70%)
Current determination of dengue disease cases in Malaysia is by clinical diagnosis, using the WHO 1997 criteria for DF and dengue haemorrhagic fever (DHF)
The population of Malaysia in 2012 was estimated to be 28,855,000
Malaysia is a federation separated into two regions by the South China Sea. There are 11 states and two federal territories on Peninsular Malaysia and two states and one federal territory in East Malaysia. The Peninsular states are divided into districts. On Borneo, the Sabah and Sarawak districts are grouped into divisions.
This article describes the national and regional epidemiology of dengue disease in Malaysia reported in the literature from 2000 to 2012. It aims to identify gaps in epidemiological knowledge and future research needs. Incidence (by age and sex), seroprevalence and serotype distribution, and other relevant epidemiological data are described.
The overall methodology, search strategy, and inclusion and exclusion criteria for this literature analysis and review are included in a protocol that was developed by a Literature Review Group (LRG). The protocol was based on the preferred reporting items of systematic reviews and meta-analyses (PRISMA) guidelines
The LRG guided the literature analysis process, defined the search strategy, and prepared the protocol and review documents. Search strings for each database were designed with reference to the expanded Medical Subject Headings thesaurus, encompassing the terms ‘dengue’, ‘epidemiology’, and ‘Malaysia. Different search string combinations were used for each electronic database with the aim of increasing the query's sensitivity and specificity.
The protocol directed that only studies published in English during the survey period (1 January 2000 to 23 February 2012) were to be included in the analysis. For databases that did not allow language and/or date limitations, references not meeting these criteria were deleted manually at the first review stage. No limits were imposed by sex, age, and race of study participants or by study type, although single-case reports were excluded, as were studies that only reported data for the period before 1 January 2000. To avoid duplicate publication of data, literature reviews and editorials utilising previously published peer-reviewed data were excluded. Unpublished reports were included if they were identified in one of the sources listed above. Finally, publications not identified by the approved search strategy and unpublished data sources that met the inclusion criteria were included if recommended by members of the LRG.
Searches of published literature were conducted for epidemiological studies of dengue disease between 9 February 2012 and 23 February 2012, in the following databases: PubMed, Excerpta Medica Database (EMBASE), MedLine, WHO Library database (WHOLIS), WPRO, Index Medicus for South-East Asia Region (IMSEAR), and the Malaysian Ministry of Health (MoH) official bulletins. Literature relating to key congresses, grey literature such as lay publications, Dengue Bulletins, and theses, and general internet searches were conducted to complement data gathered in the published literature. General internet searches were limited to the first 50 results.
We utilised an inclusive search strategy to find papers, theses, dissertations, reports and statistical tables, as well as to official web sites and grey materials. The Literature Review Group defined the inclusion/exclusion criteria and guided the search and selection process. Decisions were made by reaching a consensus via teleconferences. It was expected that the resulting articles would be heterogeneous with respect to data selection, and classification of cases, and would not be methodologically comparable. We therefore planned not to perform a meta-analysis.
After removing duplicate citations, the Literature Review Group reviewed the titles and abstracts. The full text any published sources selected was retrieved electronically or in paper form and a second review was performed to make the final selection of relevant sources to include. Sources were reviewed by the Literature Review Group to ensure they complied with the search inclusion and exclusion criteria. In particular, single-case reports and studies conducted before or after the defined search period were excluded, as were publications of duplicate data sets, unless the articles were reporting different outcome measures.
We chose not to exclude articles and other data sources nor formally rank them on the basis of the quality of evidence. Whilst we recognize that assessing study quality can potentially add value to a literature review, the consensus of the Literature Review Group was that given the expected high proportion of surveillance data among the available data sources and the nature of surveillance data (passive reporting of clinically-suspected dengue), such quality assessment would not add value to our review.
The selected data sources were collated and summarized using a data extraction instrument developed as a series of Excel (Microsoft Corp., Redmond, WA) spreadsheets. Data from literature reviews of previously published peer-reviewed studies and pre-2000 data published within the search period were not extracted. The original data sources and the extraction tables were made available to all members of the Literature Review Group for review and analysis. A narrative synthesis of our findings is presented.
A protocol amendment was prepared to allow analysis of data on file at the Malaysian MoH up to July 2012. The Vector Borne Disease Sector of the MoH provided the LRG with additional data on dengue disease epidemiology from 2000 to 2012 on 10 July 2012
This review concentrates on national epidemiological data, including the latest unpublished data received from the Malaysian MoH
All references identified in the on-line database searches were assigned a unique identification number. Following the removal of duplicates and articles that did not satisfy the inclusion criteria from review of the titles and abstracts, the full papers of the first selection of references were retrieved either electronically or in paper form. A further selection was made based on review of the full text of the articles. EMBASE, Excerpta Medica Database; PRISMA, preferred reporting items of systematic reviews and meta-analyses; WHO IMSEAR, World Health Organization Index Medicus for South-East Asia Region; WHO WHOLIS, World Health Organization Library Database; WHO SEAR MALAYSIA, World Health Organization Regional Office for Southeast Asia Malaysia; WHO WPRO, World Health Organization Western Pacific Region.
The population of Malaysia has risen by 23% since 2000, from 23,495,000 in 2000 to 28,855,000 in 2012
(A) Number of reported dengue disease cases (incidence per 100,000 population shown as numbers for the total cases only). (B) Number of reported deaths. (C) CFRs. The total annual number of dengue disease cases reported in Malaysia increased between 2000 and 2010 and decreased in 2011. Between 2000 and 2010, the incidence rate of dengue disease was consistently high (above 125 per 100,000 population). The majority of dengue disease cases were reported as DF and the ratio of DF to DHF cases remained fairly constant. The number of annual deaths from dengue disease increased between 2000 and 2010. However, after 2000 the CFR for DF+DHF remained fairly constant. CFR, case fatality rate; DF, dengue fever; DHF dengue haemorrhagic fever.
The majority of dengue disease cases were reported as DF, rising from 6692 in 2000 to 42,140 in 2010, the numbers closely matching those of the total cases. The total number of annual DHF cases also increased, from 411 in 2000 to 4031 in 2010 (
The annual number of deaths from dengue disease increased from 45 in 2000 to 134 in 2010, although the case fatality rate (CFR) remained constant at 0·2–0·3%, with 0·63% reported for the year 2000 (
The data we collected indicate that number of reported cases of dengue disease declined in children but was more stable in adults during the review period. Similar age distributions were reported for both males and females and in the Malay and Indian racial groups, with the highest proportion of dengue disease cases occurred in people aged 10–29 years
National data published by the WHO for the period 2000–2008 demonstrated that there was a predominance of males with dengue disease (55–62%). This relationship was confirmed by the proportion of males with dengue disease in all years being significantly greater (p<0·001) than the proportion of males in the population (50·8% in 2000)
Data reported for the period 2000–2011 among the different racial groups living in Malaysia demonstrated that the distribution of dengue disease by race broadly reflected the racial distribution of the country as a whole, except in the years 2003 and 2004
A case–control study conducted in Johor Bahru in south peninsular Malaysia demonstrated that the only socio-demographic factors linked significantly to dengue disease were unmarried status (p = 0.006), not wearing long-sleeved clothes (p = 0.047), and not having window screens (p = 0.002). There was no relationship demonstrated among the patients with dengue disease for age, sex, race, educational level, or type of occupation
Regional studies conducted throughout Malaysia showed that the amount of rainfall, temperature, and humidity were all directly linked to dengue disease outbreaks
For 2007, dengue disease incidence data were available for all 14 Malaysian states. Regionally, the west peninsular states of Malaysia were most affected by dengue disease. Incidence rates in Kuala Lumpur, Selangor, Kelantan, and Penang areas were 455·7, 320·3, 224·5, and 204·5 per 100,000 population, respectively; with the exception of Pahang (179·1 per 100,000 population) the remaining states were less affected (<140 per 100,000 population) and incidence rates in south peninsular area (Malacca and Johor) and the Borneo states were <105 per 100,000 population
Regional epidemiological data from Kelantan in 2003
In a national cross-sectional study conducted in 2008, 91.6% of adults aged 35–74 years were DENV seropositive and the rate increased with age (from 80% in 35–44-year-olds to 94% in 55–74-year-olds)
National data demonstrated that the dominant DENV serotypes circulating in the country changed continually during 2000–2011, from DENV-2 in 2000, to DENV-3 in 2001–2002, DENV-1 in 2003–2005, DENV-2 in 2006–2009, and DENV-1 in 2010–2011 (
(A) National data 2000–2012
Interestingly, the latest regional data from 1 January 2012 to 12 July 2012 reported in the Sentinel Surveillance System showed a heterogeneous distribution of DENV serotypes in the separate states (
This article provides a comprehensive overview of the evolving epidemiology of dengue disease in Malaysia over the period 2000–2012, despite there being some gaps in the information. As expected, the national data collated for our study and as reported recently by Mia et al.
Towards the end of the 20th century and into the 21st century, the peak age group for reported dengue disease cases has been predominantly young adults. There was a slow increase in seroprevalence rates (slower than in other countries)
There was a male predominance in the incidence data of reported dengue disease for the period 2000–2011
Up to the year 2000, most cases of dengue disease (70–80%) were reported in the urban population, particularly in working- and school-age groups
Our analysis reveals that all four DENV serotypes were found to be co-circulating in Malaysia during the period 2000–2012, although the predominant serotypes varied over time, both nationally and within the individual states
From this analysis, it is clear that recent improvements in the national surveillance system have contributed to an improvement in epidemiological knowledge in Malaysia. Nevertheless, some gaps in epidemiological knowledge still exist; for example, there is a lack of data on age-stratified seroprevalence, long-term regional incidence and serotype distribution, relationships between age and disease severity, and hospital admissions. Furthermore, the national surveillance data are likely to have underestimated the true incidence of the disease in Malaysia owing to the use of a passive reporting system and low levels of reporting from private or primary care
This literature survey and analysis reveals the changing epidemiology of dengue disease in Malaysia over the period 2000–2012 and demonstrates the consistency of the data collected. The substantial number of articles screened to identify relevant publications (over 200) and the comprehensive data extraction method used to capture the data both add strength to the results of this study.
However, there are limitations to this study, including the epidemiological knowledge gaps discussed above, which make it difficult to compare the epidemiology of the disease over time and between different geographical areas and different age groups. Furthermore, the data in this study were largely assessed based on national surveillance systems and are therefore subject to the limitations inherent to passive surveillance data, such as under-reporting, misreporting, and reporting biases. Passive reporting is clearly important for the identification of disease patterns and to guide vector control measures, but it may not be enough by itself to monitor progress in dengue disease control. The WHO 2011 revision of its 2009 dengue disease guidance
Dengue disease remains a major public health concern in Malaysia and is likely to remain endemic for a long time. There has been an increase in the incidence of all forms of dengue disease over 2000–2012. The predominant age group for dengue disease was young adults. Outbreaks tend to follow changes in predominant circulating DENV serotypes. Increasing levels of rainfall, humidity, temperature, and urbanization are also risk factors for outbreaks.
Malaysia has instituted improvements to its surveillance system that will, if continued and followed vigorously over the next few years, enable us to understand the true burden of dengue disease and to monitor the impact of dengue disease control measures in the future.
Evidence table for citations fulfilling the inclusion and exclusion criteria for the literature review (n = 28).
(PDF)
Dengue disease cases and incidence in Malaysia: national data.
(PDF)
Dengue-related deaths and case-fatality rates in Malaysia: national data.
(PDF)
PRISMA 2009 checklist.
(PDF)
The authors take full responsibility for the content of this contribution and thank Peter Blakeborough and Graham Joint (Communigen Ltd) for assisting with the preparation of manuscript drafts (supported by Sanofi Pasteur).
The authors would like to thank Gee Marsh (Sanofi Pasteur) for provision of critical comments and suggestions on the drafts, as well as Shunitra Chandrasegran for critical comments.