Dengue fever (DF) has been endemic in Malaysia since 1902 and reached epidemic proportions in 1973. The incidence rate of the disease in 1973 was 5.4 cases per 100,000 and reached 10.4 cases per 100,000 in 1987. The Chinese are the main ethnic community affected showing an overall morbidity rate of 9.0 cases per 100,000 followed by Malays 2.9 cases per 100,000 and Indians 2.4 cases per 100,000. The ethnic race ratio between Chinese, Malays and Indians which was 3.7:1:1.3 in 1975 reached 3.7:1:0.9 in 1987. The attack rates were observed to be higher in the males. The mean male:female ratio among Chinese was 1.1:1, while for Malays and Indians it was 1.5:1. The age-specific morbidity rate was highest in the 10- to 19-year age group followed by the 20- to 29-year age group. Epidemics of dengue fever were found to occur seasonally with the appearance of two peaks, viz. one in June and the other in August. Dengue fever, a rural disease before, has established itself as an urban disease.
Publication year=1992-1993
Dengue hemorrhagic fever (DHF), though endemic in the sixties, emerged as a major public health problem in Malaysia from 1973 onwards. The incidence rate of DHF which was 10.1 per 100,000 in 1973 has fallen down to 1.9 per 100,000 in 1987 with a mean case fatality rate of 6.4 per 100 persons. The Chinese appear to be more prone to DHF with the highest mean morbidity rate of 5.5 per 100,000 and case fatality rate of 6.1%. The incidence of DHF is higher in the males with a higher case fatality rate in females. Male Chinese appear to be mainly affected. The overall age-specific incidence rate is highest in two age groups, viz. 5-9 years and 10-19 years of age with a mean morbidity rate of 4.9 cases per 100,000. The mean age-specific case fatality rate was highest in the 0-4 years age group. Dengue hemorrhagic fever is predominantly an urban disease in Malaysia with a mean incidence rate of 5.3 cases per 100,000 as opposed to 1.2 cases per 100,000 being reported from rural areas. The mean overall incidence of deaths in the urban area is 0.5 compared to 0.1 per 100,000 for rural areas. There is a marked seasonal correlation between DHF cases and rainfall, with a peak in August. While all four serotypes of dengue viruses are found in Malaysia, Den 2 appears to be isolated with greater frequency during all the epidemics.
Publication year=1992-1993
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 nucleic acid sequences of the pre-membrane/membrane and envelope protein genes of 23 geographically and temporally distinct dengue (DEN)-3 viruses were determined. This was accomplished by reverse transcriptase-PCR amplification of the structural genes followed by automated DNA sequence analysis. Comparison of nucleic acid sequences revealed that similarity among the viruses was greater than 90%. The similarity among deduced amino acids was between 95% and 100%, and in many cases identical amino acid substitutions occurred among viruses from similar geographical regions. Alignment of nucleic acid sequences followed by parsimony analysis allowed the generation of phylogenetic trees, demonstrating that geographically independent evolution of DEN-3 viruses had occurred. The DEN-3 viruses were separated into four genetically distinct subtypes. Subtype I consists of viruses from Indonesia, Malaysia, the Philippines and the South Pacific islands; subtype II consists of viruses from Thailand; subtype III consists of viruses from Sri Lanka, India, Africa and Samoa; subtype IV consists of viruses from Puerto Rico and the 1965 Tahiti virus. Phylogenetic analysis has also contributed to our understanding of the molecular epidemiology and worldwide distribution of DEN-3 viruses.
By a combination of PCR and direct-cycle sequencing using consensus primers, we analyzed approximately 400-bp fragments within the NS3 genes of twenty-one dengue virus type 3 strains isolated from five neighboring Southeast Asian countries at different time intervals from 1956 to 1992. The majority of base disparities were silent mutations, with few predicted amino acid substitutions, thus emphasizing the strict conservation of the NS3 gene. Phylogenetic trees constructed on the basis of these nucleotide differences revealed distinct but related clusters of strains from the Philippines, Indonesia, and strains from Singapore and Malaysia of the 1970s and early 1980s, while the Thai cluster was relatively more distant. This genetic relationship was compatible with that proposed by other workers who have studied other dengue 3 virus genes such as E, M and prM. However, we observed that the more recent, epidemic-associated dengue 3 strains from Singapore and Malaysia of the late 1980s and early 1990s were more closely related to the Thai cluster, implying their evolution from the latter, and emphasizing the importance of viral spread via increasing travel within the Southeast Asian area and elsewhere. Nucleotide sequence analysis of the NS3 genes of dengue viruses can serve to advance the understanding of the epidemiology and evolution of these viruses.
A retrospective study involving 102 adults with dengue haemorrhagic fever (DHF) was conducted to investigate the demographic aspect, clinical presenting features, laboratory investigations, complications, and mortality associated with the disease. The clinical diagnosis of DHF was in accordance with WHO recommendations. Epistaxis, gingivitis, haematemesis and gastritis were among the common complications. Platelet levels tended to decline from a higher value on admission (mean 67,000/mm3) to lower levels on subsequent days, with the lowest (mean 61,000/mm3) being on day 6 of the fever. Hyponatraemia (46.8%) was commonly observed. Morbidity of DHF was significant (29.4%) but the case fatality rate remained low (2.0%) in our adults, suggesting that adults are less likely than children to suffer from shock syndrome.
The relationship between the Breteau index, the House index, and the occurrence of dengue/dengue hemorrhagic fever in the 6 zones of Kuala Lumpur was studied throughout 1994. Cases of dengue/dengue hemorrhagic fever varied between zones and between months, ranging from 0 to 21 cases. In most of the zones in Kuala Lumpur, the occurrence of dengue/dengue hemorrhagic fever has no relationship with the Breteau and House indices. Cases of dengue/dengue hemorrhagic fever occurred in all zones despite the low Breteau and House indices.
BACKGROUND: Dengue has been recognized as a potential hazard to tourists. A prospective, controlled study in the outpatient clinic of a German infectious disease clinic was conducted to assess the prevalence of dengue virus infection among international travelers.
METHODS: Serum samples from 130 patients with signs or recent history clinically compatible with dengue (fever, headache, muscle and joint pain, or rash), 95 matched controls with diarrhea, and 26 patients who never visited a country endemic for dengue were investigated.
RESULTS: Nine (6.9%) of the 130 patients with compatible symptoms and 1 (1%) of the 95 controls with diarrhea developed rising antibody titers against dengue virus. Of these 10 patients with probable dengue infection, 6 had been to Thailand, 2 to Malaysia, and 1 each to Indonesia and Brazil.
CONCLUSIONS: Infection with dengue virus appears to be a realistic threat to travelers to Southeast Asia. Symptoms commonly associated with dengue, such as fever, myalgia, arthralgia, and vomiting, can be helpful for diagnosis when present, but the absence of typical symptoms does not exclude infection.
About two-thirds of the world's population live in areas infested with dengue vectors, mainly Aedes aegypti. All four dengue viruses are circulating, sometimes simultaneously, in most of these areas. It is estimated that up to 80 million persons become infected annually although marked underreporting results in the notification of much smaller figures. Currently dengue is endemic in all continents except Europe and epidemic dengue haemorrhagic fever (DHF) occurs in Asia, the Americas and some Pacific islands. The incidence of DHF is much greater in the Asian countries than in other regions. In Asian countries the disease continues to affect children predominantly although a marked increase in the number of DHF cases in people over 15 years old has been observed in the Philippines and Malaysia during recent years. In the 1990's DHF has continued to show a higher incidence in South-East Asia, particularly in Viet Nam and Thailand which together account for more than two-thirds of the DHF cases reported in Asia. However, an increase in the number of reported cases has been noted in the Philippines, Lao People's Democratic Republic, Cambodia, Myanmar, Malaysia, India, Singapore and Sri Lanka during the period 1991-1995 as compared to the preceding 5-year period. In the Americas, the emergence of epidemic DHF occurred in 1981 almost 30 years after its appearance in Asia, and its incidence is showing a marked upward trend. In 1981 Cuba reported the first major outbreak of DHF in the Americas, during which a total of 344,203 cases of dengue were notified, including 10,312 severe cases and 158 deaths. The DHF Cuban epidemic was associated with a strain of dengue-2 virus and it occurred four years after dengue-1 had been introduced in the island causing epidemics of dengue fever. Prior to this event suspected cases of DHF or fatal dengue cases had been reported by five countries but only a few of them fulfilled the WHO criteria for diagnosis of DHF. The outbreak in Cuba is the most important event in the history of dengue in the Americas. Subsequently to it, in every year except 1983, confirmed or suspected cases of DHF have been reported in the Region. The second major outbreak in the Americas occurred in Venezuela in 1989 and since then this country has suffered epidemics of DHF every year. Between 1981 and 1996 a total of 42,246 cases of DHF and 582 deaths were reported by 25 countries in the Americas, 53% of which originated from Venezuela and 24% from Cuba. Colombia, Nicaragua and Mexico have each reported over 1,000 cases during the period 1992-1996. About 74% of the Colombian cases and 97% of the Mexican cases were reported during 1995-1996. A main cause of the emergence of DHF in the Americas was the failure of the hemispheric campaign to eradicate Aedes aegypti. Following a successful period that resulted in the elimination of the mosquito from 18 countries by 1962, the programme began to decline and as a result there was a progressive dissemination of the vector so that by 1997 with the exception of Canada, Chile and Bermuda, all countries in the Americas are infested. Other factors contributing to the emergence/re-emergence of dengue/DHF include the rapid growth and urbanization of populations in Latin America and the Caribbean, and increased travel of persons which facilitates dissemination of dengue viruses. Presently, all four dengue serotypes are circulating in the Americas, thus increasing the risk for DHF in this region.
The limited sequencing approach was used to study the molecular epidemiology of 24 Malaysian dengue 2 viruses which were isolated between 1968 and 1993. The sequences of a 240-nucleotide-long region across the envelope/non-structural 1 protein (E/NS1) gene junction of the isolates were determined and analysed. Alignment and comparison of the nucleotide and deduced amino acid sequences of the isolates revealed that nucleotide changes occurred mostly at the third position of a particular codon and were of the transition (AG, CU) type. Five nucleotide changes resulted in amino acid substitutions. Pairwise comparisons of the nucleotide sequences gave divergence values ranging from 0 to 9.2%. At the amino acid level, the divergence ranged between 0 and 3.8%. Based on the 6% divergence as the cut-off point for genotypic classification, the isolates were grouped into two genotypes, I and II. Comparison of the nucleotide sequences of the Malaysian dengue isolates with those of the dengue viruses of other regions of the world revealed that members of genotypes I and II were closely related to viruses from the Indian Ocean and Western Pacific regions, respectively.
To characterize the dengue epidemic that recently occurred in Malaysia, we sequenced cDNAs from nine 1993-1994 dengue virus type-3 (DEN-3) isolates in Malaysia (DEN-3 was the most common type in Malaysia during this period). Nucleic acid sequences (720 nucleotides in length) from the nine isolates, encompassing the precursor of membrane protein (preM) and membrane (M) protein genes and part of the envelope (E) protein gene were aligned with various reference DEN-3 sequences to generate a neighbor-joining phylogenetic tree. According to the constructed tree, the nine Malaysian isolates were grouped into subtype II, which comprises Thai isolates from 1962 to 1987. Five earlier DEN-3 virus Malaysian isolates from 1974 to 1981 belonged to subtype I. The present data indicate that the recent dengue epidemic in Malaysia was due to the introduction of DEN-3 viruses previously endemic to Thailand.
Dengue continues to be a major health threat to Malaysia a century after its first reported outbreak in 1902. Examination of the available outbreak data suggested that a major DF/DHF outbreak occurred in Malaysia in a cyclical pattern of approximately every 8 years. All four dengue virus serotypes are found co-circulating in Malaysia, but after the first and only major outbreak involving DEN-4 in 1960's, only DEN-1, DEN-2 and DEN-3 were associated with DF/DHF outbreaks. It is argued that perhaps the spread of the later dengue virus serotypes followed the pattern of spread of the mosquito vector Aedes aegypti, whereas the former was associated with Aedes albopictus, the outdoor and rural area dwelling mosquito. Estimating from the trend and pattern of dengue and the associated dengue virus serotypes, unless there is a major breakthrough in dengue vaccine development, it is likely that dengue outbreaks will continue to occur in Malaysia throughout the 21st century.