Dengue is a major public health concern worldwide, with the number of infections increasing globally. The illness imposes the greatest economic and human burden on developing countries that have limited resources to deal with the scale of the problem. No cure for dengue exists; treatment is limited to rehydration therapy, and with vector control strategies proving to be relatively ineffective, a vaccine is an urgent priority. Despite the numerous challenges encountered in the development of a dengue vaccine, several vaccine candidates have shown promise in clinical development and it is believed that a vaccination program would be at least as cost-effective as current vector control programs. The lead candidate vaccine is a tetravalent, live attenuated, recombinant vaccine, which is currently in Phase III clinical trials. Vaccine introduction is a complex process that requires consideration and is discussed here. This review discusses the epidemiology, burden and pathogenesis of dengue, as well as the vaccine candidates currently in clinical development.
Nipah virus, a newly emerging deadly paramyxovirus isolated during a large outbreak of viral encephalitis in Malaysia, has many of the physical attributes to serve as a potential agent of bioterrorism. The outbreak caused widespread panic and fear because of its high mortality and the inability to control the disease initially. There were considerable social disruptions and tremendous economic loss to an important pig-rearing industry. This highly virulent virus, believed to be introduced into pig farms by fruit bats, spread easily among pigs and was transmitted to humans who came into close contact with infected animals. From pigs, the virus was also transmitted to other animals such as dogs, cats, and horses. The Nipah virus has the potential to be considered an agent of bioterrorism.
Emerging and re-emerging infectious diseases have become a major global problem. Malaysia appears to be an epicenter for such infections and in recent years, several outbreaks have occurred resulting in loss of lives and economic hardships. In this paper, we discussed the outbreaks of leptospirosis, enterovirus 71 encephalitis, chikungunya polyarthritis and Nipah encephalitis and how a developing country such as Malaysia managed the situation with the help of international agencies and organisations. Many valuable lessons were learned and by sharing our experience, it is hoped that we will be in a better position to handle future outbreaks and prevent their spread to countries in the region.
Viral infections are probably the most important cause of childhood morbidity and mortality in the world. In many developing countries in South East Asia and the Western Pacific, priority health problems include acute respiratory infections, acute diarrhoeas and arboviral infections. Where studies have been carried out, there is no significant difference in the aetiological agents involved or in the manifestation of clinical childhood disease. Surveillance of these diseases have improved with the introduction of rapid viral diagnosis. The better understanding of the immunopathogenesis of many diseases have also encouraged research in this area and will lead to the better control and management of these diseases. However, the search for antivirals has been disappointing but fortunately new vaccines are on the horizon and the prospect for bringing some of these diseases under control through vaccination are bright.
Rubella antibody rates in the female population of Kuala Lumpur were lower than those reported from temperate countries, though similar to rates found in other tropical countries excepting Singapore. Among the major ethnic groups, the immunity status of the Chinese was higher than that of the Malay and Indian groups.
Since dengue was first documented in Malaysia in 1902 and made notifiable in 1973, the disease pattern has changed from major outbreaks every four years to one of increasing trend yearly. The largest outbreak was seen in 1996 with 14,255 dengue cases reported and 32 deaths. The case fatality rate varied from a high of 10.43% in 1985 when dengue type 3 was the predominant type to a low of 1.29% when dengue type 1 predominated. Severe disease patterns have been observed with dengue 2 and 3 serotypes in the country. The clinical spectrum has also been changing and multisystem involvement with more severe manifestations are being seen. Liver involvement has been documented since 1987. Fulminant hepatitis with encephalopathy can resemble Reye's syndrome. Dengue type 3 has been isolated from liver biopsy specimens. Neurological manifestations can very from irritability, convulsions, coma to peripheral neuritis. The isolation of dengue viruses from cerebrospinal fluids recently strongly suggests that dengue viruses can be neurovirulent. Adult respiratory distress syndrome was seen in three children admitted with shock. Deaths were more frequent in children in the early period but since 1982, over 50% of deaths have occurred in patients over the age of 15 years.
The control of dengue outbreak requires a multi-pronged effort by the various government agencies. It requires co-operation of the community in the control activities, strict adherence to existing control procedures and guidelines by health personnel, increased manpower where necessary and strengthening co-operation between various health agencies to prevent delay in instituting control measures.
1. Anaesthesia caused marked decreases in the plasma concentrations of triiodothyronine (T3) and thyroxine (T4) and in the body temperature of young fowl. 2. Exogenous T4 or a thyroid hormone secretagogue (somatostatin antiserum), increased endogenous T3 and T4 concentrations and body temperature in conscious birds and prevented the body temperature decline in anaesthetized fowl. 3. These results provide further evidence for a role of T3 and T4 in temperature regulation in birds, particularly during anaesthesia.
Emerging infectious diseases involving zoonosis have become important global health problems. The 1998 outbreak of severe febrile encephalitis among pig farmers in Malaysia caused by a newly emergent paramyxovirus, Nipah virus, is a good example. This disease has the potential to spread to other countries through infected animals and can cause considerable economic loss. The clinical presentation includes segmental myoclonus, areflexia, hypertension, and tachycardia, and histologic evidence includes endothelial damage and vasculitis of the brain and other major organs. Magnetic resonance imaging has demonstrated the presence of discrete high-signal-intensity lesions disseminated throughout the brain. Nipah virus causes syncytial formation in Vero cells and is antigenically related to Hendra virus. The Island flying fox (Pteropus hypomelanus; the fruit bat) is a likely reservoir of this virus. The outbreak in Malaysia was controlled through the culling of >1 million pigs.
Rapid diagnosis of dengue infection is essential to patient management and disease control. The development of a rapid (5 min) immunochromatographic test and a 2 h commercial capture enzyme linked immunosorbent assay (ELISA) for anti-dengue IgM and IgG antibodies may lead to more rapid and accurate testing in peripheral health settings and diagnostic laboratories.
In 1990 and 1991, six laboratories located in the WHO Western Pacific Region (WPR) and South East Asian Region (SEAR) were selected, based on their experience in the immunofluorescence antibody technique (IFAT), to participate in the evaluation of a WHO monoclonal antibody (Mab) kit to detect respiratory syncytial (RS) virus, influenza A virus, influenza B virus, parainfluenza virus and adenovirus. Despite differences in the initial standardization procedures, the WHO monoclonal antibodies were found to be of high quality, sensitivity and specificity when tested on clinical specimens. The constant supply of affordable high quality reagents from WHO would enable their use in clinical virological laboratories in the developing countries as well as promote the utilization of IFAT as an adjunct to cell culture isolation in the diagnosis of acute respiratory viral infections.
In recent years, a large amount of nucleotide sequence data for dengue viruses has been published. Most of it was derived by sequencing cDNA synthesized from highly purified genomic viral RNA. This paper presents a simple and rapid method for the isolation of total RNA from mosquito cells infected with dengue viruses. This RNA can be used for direct nucleotide sequencing with specific primers without the need for further purification.
A study was carried out at the University Hospital, Kuala Lumpur, Malaysia to determine the age-specific prevalence of measles infection by serology and the age specific - seroconversion rates following measles vaccination. The results show that the percentage of children with passively acquired measles antibodies decreased with increasing age fill three to five months of age. From 12 months of age, the percentage of positivity increased sharply due probably to natural infection. The geometric mean antibody titre was low at birth, but from six months it started to increase. These results indicate that measles infection is common in Malaysia and a small number of children began to acquire natural measles infection from six to eight months of age; however the peak age for the acquisition of measles infection was from 12 months to five years of age. Seroconversion rates following vaccination from nine months of age, ranged from 94-99%. However, the rates and the geometric mean titre were higher among those vaccinated at 11 months of age or older compared with those vaccinated at nine or ten months of age. Based on the above results, it is concluded that the optimum age for measles immunization in Malaysia should be 11 months.
A modification of the IgM-capture ELISA which can provide an early diagnosis for dengue infection is presented. The test is technically simple compared to HI and appears to be more sensitive. It has the advantage over HIT for the detection of specific IgM in that it is more sensitive and the reading of the result is not subjective. There is the possibility of the test being able to replace HI and HIT in the future.
Two patients with idiopathic multitudinous fundic gland polyposis, a hitherto undescribed condition, were reported. They presented incidentally with a multitude of fundic gland polyps, 52 and 147, without a family history of polyposis, and these polyps were not attributable to the chronic use of proton pump inhibitors. All polyps were removed by hot-biopsy polypectomy, and each was individually subjected to pathological examination, which showed no evidence of dysplasia. When confronted with gastric polyps of clinically undetermined origin, endoscopists would, to exclude dysplasia, usually resect all if they are few and sample some and survey the others periodically if they are numerous. The condition reported presents a management dilemma: Because the number of the polyps is such that they are manageable by total polypectomy, should this be carried out, despite the labor intensiveness involved, to exclude dysplasia, and are the polyps a variant of syndromic polyposis and therefore carry a malignant potential and inform the need for periodic surveillance and to investigate the patient's kindred? The frequency of this condition and whether it is truly not associated with dysplasia require further studies.
Stool samples from healthy children mainly of the low income group aged 0 to 7 years of age from five Maternal and Child Health Centres in Kuala Lumpur were obtained for isolation of enteroviruses. The specimens were collected before and after the mass vaccination given in the face of polio type 1 epidemic which started in October, 1971. The prevelance rate of enteroviruses was 11.9% (3.0% polioviruses, 8.9% non-polio enteroviruses) before the vaccination and essentially the same after. Coxsackie A viruses predominated over the other enteroviruses in the pre- and post-vaccination phases. The highest isolation rate of enteroviruses was observed in children 0 to 2 years age. No significant differences in distribution by sex, race and month were noted. A sharp fall in the prevalence rates of total enteroviruses and polioviruses was noted shortly after the mass vaccination campaign However, the rates reverted to the pre-vaccination state during the next successive years.
A simple, rapid and objective infectivity assay based on an in situ enzyme immunoassay (EIA) was developed for the fast-growing and cytopathic cell culture-adapted hepatitis A virus (HAV) strain HM175A.2. Infectivity titration by EIA correlated well with titration by cytopathic effects. The reliability of this assay was demonstrated by close agreement in virus infectivity titers among different assays of the same virus aliquot and between assays of different virus aliquots. HAV infected cell cultures after fixation could be stored for up to 1 week before testing without decline in virus titer.