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PubMed2005

A review of dengue fever incidence in Kota Bharu, Kelantan, Malaysia during the years 1998-2003.

Dengue is the most common and widespread arthropod borne arboviral infection in the world today. It is estimated that there are at least 100 million cases of dengue fever (DF) annually and 500,000 cases of dengue hemorrhagic fever (DHF) which require hospitalization. In Malaysia, it has become a major public health problem. Malaysia recorded 19,544 dengue cases in 1997, the highest recorded since the disease was made notifiable in the country. Of 19,544 cases, 806 were DHF with 50 deaths. The objectives of this analysis were to describe the incidence of dengue fever and dengue hemorrhagic fever in Kota Bharu, Kelantan, Malaysia for the years 1998-2003 and to explore the characteristics of dengue fever and dengue hemorrhagic fever in Kota Bharu, Kelantan, Malaysia for years 1998-2003. A total of 4,716 dengue cases were notified involving 4,476 (94.9%) DF and 240 (5.1%) DHF cases, which increased though the years. The highest incidence was in January (701 or 14.9%), while the lowest was in May (188 or 4.0%). Forty percent of cases (n=1,890) were in the 15-29 year old group. The Majority were Malays (4,062 or 86.1%) and 2,602 or 55.2% were male. A total of 4,477 cases (95%) were local cases and 4,289 or 91% came from the urban area. For priority areas, 3,772 (80%) were from priority 1. More than half the cases had positive serology results. All symptoms occurred in more than 96% of cases and fever was the commonest (99.7%). The mean values for age, temperature, systolic and diastolic blood pressure (BP) were 27.8 +/- 15.4 years, 37.9 +/- 0.90 degrees C, 115 +/- 15.2 mmHg and 73 +/- 11.1 mmHg, respectively. The mean value for the time interval between the onset of symptoms and diagnosis, onset of symptoms and notification and time of diagnosis to notification were 5.1 +/- 2.3, 5.9 +/- 2.5 and 0.8 +/- 1.1 days, respectively. There were associations between the types of dengue and classification, area and priority area. Among the symptoms, the association was only seen in joint pain. The mean significant differences between DF and DHF were found in age and systolic blood pressure. The incidence of dengue in Kota Bharu is comparable to that in Malaysia. The increase in the number of cases needs to be addressed promptly with effective surveillance, prevention and control programs.

Adolescent↗
PubMed1985

Rainfall, abundance of Aedes aegypti and dengue infection in Selangor, Malaysia.

An epidemio-meteorotropic analytical study of Selangor, in the Southwest coast of Peninsular Malaysia, examines the monthly incidence of dengue for the period 1973-1982 to assess possible quantitative association with the monthly rainfall. The relationships between rainfall, abundance of A. aegypti and dengue infection during 1982 in Jinjang, a dengue-prone area in Selangor, were also examined. A quantitative association between rainfall and the number of dengue cases was found during the first wet period. The lag time between the onset of heavy rain and dengue outbreak was about two to three months. A 120% increase in the number of dengue cases was observed when the monthly rainfall was 300 mm or more. Positive associations were seen between the incidence of dengue and the Aedes house index and the Breteau index in Jinjang. The relationships between these three variables and rainfall suggest that the latter might have exerted its effect on dengue infection partly through the creation of more breeding sites for A. aegypti. Assessment of the importance of A. aegypti in the transmission of dengue in this locality was not possible because of the lack of adjustment for A. albopictus, the other known vector of dengue in the state, and for social and other environmental factors influencing infection rates. In spite of this and the interpretational problems common in aggregate studies, the present analyses have provided relatively strong statistical evidence of an association between rainfall and dengue outbreaks in Selangor, thereby indicating that it is a factor worthy of careful surveillance and monitoring.

Aedes↗
PubMed1995

[Imported dengue fever in Switzerland--serological evidence for a hitherto unexpectedly high prevalence].

Dengue fever is probably the most important arthropod-borne viral infection worldwide. The World Health Organization estimates an incidence of 100 million cases per year. Dengue fever is of clinical importance mainly in tropical and subtropical zones, but the increasing number of travellers visiting these endemic areas means that physicians in temperate zones will meet this tropical infectious disease more frequently. To estimate the frequency of dengue fever in Switzerland, we retrospectively analyzed a cohort of patients in whom clinicians wished to rule out a case of malaria on the assumption that some of these patients may have been exposed to dengue virus while travelling in tropical and subtropical areas. Dengue was diagnosed by serology on contemporary stored serum samples with a commercially available assay that has been evaluated before. During the study period (1.1.93 to 1.7.94) a malaria diagnosis was requested by the physicians in our center in 87 cases and malaria was diagnosed in 10 (11.5%). In 38 of these 87 cases a stored serum sample was available for dengue serology. All of these patients had visited an area where not only malaria but dengue virus was endemic. In 7 of these 38 cases (18%) malaria was diagnosed. In 3 patients (8%) the dengue serology (IgM and IgG) was indicative of acute dengue fever. All 3 cases had clinical findings compatible with the disease. In 4 more patients (10%) anti-dengue IgG antibodies were found. All of these 4 patients had previous exposure to dengue virus but no acute clinical illness.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2001

Amino acid and phenotypic changes in dengue 2 virus associated with escape from neutralisation by IgM antibody.

Two dengue 2-specific IgM monoclonal antibodies (MAb) recognised spatially unrelated epitopes on the envelope (E) protein of dengue 2 virus, which were also recognised by serum from 20 and 50%, respectively, of patients with a primary dengue 2 infection. Dengue 2 virus populations escaping neutralisation by MAb 6B2 (representing the majority population of dengue 2-specific IgM MAbs ) had a deduced amino acid change (G-S) in the pre-Membrane (prM) protein at position 15 and a second in the E protein at E311 (E-G). The change in the E protein was adjacent to the only other epitopes on dengue 2 virus (E307, E383-385) involved in neutralisation that have been identified but that were recognised by IgG antibodies. Dengue 2 virus escaping neutralisation by IgM MAb 10F2, representing the minority population of dengue 2-specific IgM MAbs, had the same deduced amino acid change (G-S) at prM15 as the 6B2 neutralisation escape mutant dengue 2 virus population and four deduced amino acid changes in the E protein (E69, T-I, in the glycosylation motif; E71, E-D; E112, S-G; E124, I-N), which may be close enough to each other to form a single epitope and a fifth at E402 (F-L) in a region of the E protein of TBE virus essential for the low pH-induced E protein dimer-trimer transition. The 10F2 neutralisation escape mutant, but not the 6B2 one, had lost its ability to cause fusion from within Aedes albopictus mosquito cells and was inactivated more rapidly than the 6B2 neutralisation escape mutant and wild type viruses at 42 degrees C. Dengue 2 viruses passaged in BHK cells in the absence of a selecting antibody, shared a common amino acid (S) at E53, which differed from both wild type and neutralisation escape mutant virus populations at this position (P) and may have been responsible for a significant reduction in the ability of these "passage control" virus populations to be neutralised by both 6B2 and 10F2 antibodies.

Amino Acids↗
PubMed2002

Single rapid TaqMan fluorogenic probe based PCR assay that detects all four dengue serotypes.

Public health laboratories require rapid diagnosis of dengue outbreaks for application of measures such as vector control. We have developed a rapid single fluorogenic probe-based polymerase chain reaction assay for the detection of all four dengue serotypes (FUDRT-PCR). The method employs primers and probe that are complementary to the evolutionarily conserved 3' untranslated region of the dengue genome. The assay detected viral RNA of strains of all four dengue serotypes but not of the flaviviruses Japanese encephalitis virus, Murray Valley encephalitis virus, Kunjin, Stratford, West Nile, Alfuy or Yellow fever. When compared to an existing nested-PCR assay for the detection of dengue on clinical samples, FUDRT-PCR detected dengue 1 (100%, n=14), dengue 2 (85%, n=13), dengue 3 (64%, n=14) and dengue 4 (100%, n=3) with the indicated sensitivities. FUDRT-PCR enables diagnosis of acute dengue infection in four hours from sample receipt. In addition, a single-test procedure should result in a reduction in the number of tests performed with considerable cost savings for diagnostic laboratories.

3' Untranslated Regions↗
PubMed2001

Immunopathogenesis of dengue virus infection.

Dengue virus infection causes dengue fever (DF), dengue hemorrhagic fever (DHF), and dengue shock syndrome (DSS), whose pathogeneses are not clearly understood. Current hypotheses of antibody-dependent enhancement, virus virulence, and IFN-gamma/TNFalpha-mediated immunopathogenesis are insufficient to explain clinical manifestations of DHF/DSS such as thrombocytopenia and hemoconcentration. Dengue virus infection induces transient immune aberrant activation of CD4/CD8 ratio inversion and cytokine overproduction, and infection of endothelial cells and hepatocytes causes apoptosis and dysfunction of these cells. The coagulation and fibrinolysis systems are also activated after dengue virus infection. We propose a new hypothesis for the immunopathogenesis for dengue virus infection. The aberrant immune responses not only impair the immune response to clear the virus, but also result in overproduction of cytokines that affect monocytes, endothelial cells, and hepatocytes. Platelets are destroyed by crossreactive anti-platelet autoantibodies. Dengue-virus-induced vasculopathy and coagulopathy must be involved in the pathogenesis of hemorrhage, and the unbalance between coagulation and fibrinolysis activation increases the likelihood of severe hemorrhage in DHF/DSS. Hemostasis is maintained unless the dysregulation of coagulation and fibrinolysis persists. The overproduced IL-6 might play a crucial role in the enhanced production of anti-platelet or anti-endothelial cell autoantibodies, elevated levels of tPA, as well as a deficiency in coagulation. Capillary leakage is triggered by the dengue virus itself or by antibodies to its antigens. This immunopathogenesis of DHF/DSS can account for specific characteristics of clinical, pathologic, and epidemiological observations in dengue virus infection.

Animals↗
PubMedDate not supplied

The use of reverse transcription-polymerase chain reaction (RT-PCR) for the rapid detection and identification of dengue virus in an endemic region: a validation study.

Dengue is the most important arboviral disease worldwide. Dengue diagnosis is usually made by serology, but serological techniques do not identify the infecting strain, and are only useful late in the course of infection. Several reverse transcription-polymerase chain reaction (RT-PCR) protocols have been described for dengue diagnosis but none of them has been used on a regular basis. We conducted a validation study of PCR-based diagnosis in an area (in Brazil) where dengue-1 virus has been circulating at a low incidence rate. Viral detection by RT-PCR was evaluated using the sera of 253 patients with clinical diagnosis of dengue, and the results were compared to those obtained by IgM capture enzyme-linked immunosorbent assay (MAC-ELISA) and virus isolation. Out of 75 IgM-positive samples, 17 were RT-PCR positive, and only 2 were positive for virus isolation. Through enzymatic digestion of PCR amplicons, we were able to differentiate the 2 dengue serotypes circulating in Brazil (dengue-1 and dengue-2), and to determine that dengue-1 was the virus responsible for the infections. We show with this study that RT-PCR is more sensitive than virus isolation on clinical samples and allows for a rapid detection of dengue infections and for a straightforward identification of the circulating serotype.

Brazil↗
PubMed2003

Microevolution and virulence of dengue viruses.

The evolution of dengue viruses has had a major impact on their virulence for humans and on the epidemiology of dengue disease around the world. Although antigenic and genetic differences in virus strains had become evident, it is mainly due to the lack of animal models of disease that has made it difficult to detect differences in virulence of dengue viruses. However, phylogenetic studies of many different dengue virus samples have led to the association between specific genotypes (within serotypes) and the presentation of more or less severe disease. Currently, dengue viruses can be classified as being of epidemiologically low, medium, or high impact; i.e., some viruses may remain in sylvatic cycles of little or low transmissibility to humans, others produce dengue fever (DF) only, and some genotypes have been associated with the potential to cause the more severe dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) in addition to DF. Although the factors that contribute to dengue virus epidemiology are complex, studies have suggested that specific viral structures may contribute to increased replication in human target cells and to increased transmission by the mosquito vector; however, the immune status and possibly the genetic background of the host are also determinants of virulence or disease presentation. As to the question of whether dengue viruses are evolving toward virulence as they continue to spread throughout the world, phylogenetic and epidemiological analyses suggest that the more virulent genotypes are now displacing those that have lower epidemiological impact; there is no evidence for the transmission of antigenically aberrant, new strains.

Animals↗
PubMed2000

Do escape mutants explain rapid increases in dengue case-fatality rates within epidemics?

During the Cuban dengue epidemics of 1981 and 1997, significant monthly increases were observed in the proportion of total cases that presented as dengue haemorrhagic fever or dengue shock syndrome (DHF/DSS), and in case-fatality rates for both dengue fever and DHF/DSS. We believe that theses increases can be explained by the hypothesis that some of the population of antibodies against dengue 1 virus raised after natural primary infections react with "neutralisation" determinants found on dengue 2 viruses. These heterotypic antibodies do not prevent secondary dengue 2 infections, but serve to down-regulate the disease to mild illness or symptomless infections. A population of dengue 2 viruses that replicates in dengue-1-immune hosts escape heterotypic neutralisation. When inoculated into a new dengue-1-immune host, these viruses are free to interact with the more abundant infection-enhancing antibodies to produce severe disease.

Antibodies, Viral↗
PubMed1998

Microplate-reverse hybridization method to determine dengue virus serotype.

A reverse transcriptase-polymerase chain reaction (RT-PCR) and microplate-reverse hybridization method were developed to detect and type dengue viruses in patients plasma specimens. A silica method was used to isolate RNA; and 3'-noncoding region universal primers were used to amplify dengue virus RNA. Using RT-PCR and ethidium bromide staining we could detect dengue virus in serum spiked with serially diluted dengue virus with a level of sensitivity similar to that of a quantitative fluorescent focus assay of dengue viruses in cell culture, i.e. 1.4 fluorescent focus units per reaction. Applying this assay to 14 dengue-positive plasma samples and 13 dengue-negative samples, dengue viremia was detectable by RT-PCR with a sensitivity comparable to mosquito inoculation. To determine the serotypes, digoxigenin-labeled PCR products from plasma samples and six laboratory adapted dengue viruses were hybridized in stringent conditions to serotype-specific DNA probes immobilized on microplates, and the hybridized product was detected with a colorimetric assay. Serotypes of dengue viruses, in cell culture and in patient plasma specimens, were identified using this method.

Dengue↗
PubMed2001

Human dendritic cells as targets of dengue virus infection.

Dengue virus infections are an emerging global threat. Severe dengue infection is manifested as dengue hemorrhagic fever and dengue shock syndrome, both of which can be fatal complications. Factors predisposing to complicated disease and pathogenesis of severe infections are discussed. Using immunohistochemistry, immunofluorescence, flow cytometry, and ELISA techniques, we studied the cellular targets of dengue virus infection, at both the clinical (in vivo) and the laboratory (in vitro) level. Resident skin dendritic cells are targets of dengue virus infection as demonstrated in a skin biopsy from a dengue vaccine recipient. We show that factors influencing infection of monocytes/macrophages and dendritic cells are different. Immature dendritic cells were found to be the cells most permissive for dengue infection and maybe early targets for infection. Immature dendritic cells exposed to dengue virus produce TNF-alpha protein. Some of these immature dendritic cells undergo TNF-alpha mediated maturation as a consequence of exposure to the dengue virus.

Biopsy↗
PubMed1993

Dengue virus-specific, human CD4+ cytotoxic T lymphocytes generated in short-term culture.

We previously reported cytotoxic activity of dengue virus-specific CD4+ CD8- T cell clones established in long-term in vitro culture. In the present experiments we tried to determine whether dengue virus-specific CD4+ CD8- CTL3 are present in short-term bulk cultures. Peripheral blood mononuclear cells (PBMC)3 from a donor who had been immunized with an experimental live attenuated dengue 1 vaccine 8 months earlier were used. PBMC were incubated with noninfectious dengue 1 antigen (Ag)3 for 7 days, and were examined for dengue 1-specific cytotoxic activity. PBMC cultured with dengue 1 Ag lysed autologous lymphoblastoid cell line (LCL)3 pulsed with noninfectious dengue 1 Ag, but did not lyse LCL pulsed with Ag of other dengue serotype, West Nile virus, or yellow fever virus, or control Ag. Treatment of cultured PBMC with monoclonal antibody to CD3 or CD4 and complement abrogated the cytotoxic activity but treatment with a monoclonal antibody to CD8 and complement did not. A time course study showed that dengue 1 Ag-specific CTL were first detected in 5 day cultures. Lysis of target cells by these CD4+ CTL were restricted by HLA class II, and HLA DQw1 and HLA DRw52 were determined to be the restriction molecules. These results indicate that dengue virus-specific CD4+ CD8- CTL are generated in short-term bulk cultures as well as in long-term-cultured cell lines, and support the concept that CD4+ CTL may be generated in vivo during infection.

Antigens, Viral↗
PubMed2006

Patterns of disease among adults hospitalized with dengue infections.

BACKGROUND: Recent years have seen an increase in dengue infections among adults in Sri Lanka, with similar trends seen in many other countries. Data on the natural history and outcome of dengue in adults are quite limited. AIM: To study clinical and laboratory findings in adult dengue patients hospitalized in Sri Lanka during a recent major dengue epidemic. DESIGN: Prospective observational study. METHODS: Clinical, laboratory and demographic information were collected from adult patients with confirmed dengue infections (n = 108) treated in a general medical ward in Sri Lanka from 24 April to 31 July 2004. RESULTS: There were 68 male and 40 female patients, mean age 26.6 years. Dengue fever (DF) was seen in 33 (30.6%) and dengue haemorrhagic fever (DHF) in 75 (69.4%). Of the 37 (34.3%) with primary dengue infections, 19 (51.4%) developed DF and 18 (48.6%) developed DHF. Overall, 42 patients (38.9%) had bleeding manifestations. These adults showed differences in clinical and laboratory findings, disease severity and mortality, compared to children seen during the same epidemic. Secondary dengue infections were significantly associated with development of severe disease (OR 5.0, 95%CI 1.9-13.5, p < 0.001). Mortality was 3.7%. DISCUSSION: Pooling data on adult dengue patients from different regions should help us to understand the natural history of disease in this group. It would also help in developing evidence-based treatment guidelines and allocating limited and scarce health resources. Our data contribute towards this goal.

Adolescent↗
PubMed1990

Passive protection studies in mice with monoclonal antibodies directed against the non-structural protein NS3 of dengue 1 virus.

Antibody-mediated enhancement of dengue virus replication is thought to be a mechanism contributing to the pathogenesis of dengue haemorrhagic fever and dengue shock syndrome. Enhancement is associated with antibodies to structural components of the virus. To circumvent the problem of immune enhancement, studies to identify protective antigens of dengue virus have involved non-structural proteins. Passive and active protection against lethal dengue virus infection in mice have been demonstrated with the non-structural protein NS1. In this study, the dengue virus non-structural protein NS3 was examined in passive protection studies with monoclonal antibodies prepared against NS3 of dengue 1 virus (Hawaiian). Five monoclonal antibodies that were authenticated to be reactive to NS3 were used to immunize 13- to 14-day old mice intraperitoneally. Thereafter, the mice were challenged intracerebrally with 100 LD50 of neurotropic dengue 1 virus and the survival indices of the mice were calculated. Significant decreases in survival indices (P less than 0.05), indicating increases in survival times were observed with four of five monoclonal antibodies tested. Monoclonal antibodies to NS3 of dengue 1 virus are able to increase the survival time of mice challenged with a lethal dose of dengue 1 virus, although the mechanism remains to be defined.

Animals↗
PubMed1999

Evaluation of four methods for detection of immunoglobulin M antibodies to dengue virus.

Dengue has become hyperendemic in many islands of the Caribbean region. The performance in a diagnostic laboratory of four commercial assays for detection of immunoglobulin M (IgM) antibodies was evaluated. Sera from 62 patients with dengue virus infection were studied. These included 18 patients from whom dengue virus type 2 was isolated in a 1997 outbreak (specimens collected a mean of 14 days after onset of symptoms), 8 patients with dengue hemorrhagic fever (mean time after onset, 11 days), and 36 patients in whom dengue was previously confirmed by serology (mean time after onset, 10 days). Thirty serum specimens from blood donors in a country where dengue is not endemic were used as negative controls. The methods evaluated were two IgM-capture enzyme-linked immunosorbent assays (ELISA) (MRL Diagnostics, Cypress, Calif., and PanBio, Queensland, Australia), a dot ELISA dipstick assay (Integrated Diagnostics, Baltimore, Md.), and a rapid immunochromatographic assay for dengue IgG and IgM (PanBio IC). IgG antibodies were also detected by an ELISA method (MRL Diagnostics). The sensitivities of the four assays were as follows: MRL Diagnostics IgM ELISA, 98.4%; PanBio IgM ELISA, 85.5%; Integrated Diagnostics IgM dot ELISA, 96. 8%; and PanBio IC, 83.9%. The specificities of all tests were 100%. Evidence of secondary dengue was found in all patients with dengue hemorrhagic fever and in 83% of the remaining patients. The MRL Diagnostics IgM ELISA appears to be more sensitive than the PanBio IgM ELISA, and this may be significant when IgM titers are low, particularly in patients with secondary dengue infections. The dot ELISA dipstick assay is equally sensitive and may be more appropriate for use in laboratories with lower workloads.

Antibodies, Anti-Idiotypic↗
PubMed2002

Dengue virus selectively induces human mast cell chemokine production.

Severe dengue virus infections usually occur in individuals who have preexisting anti-dengue virus antibodies. Mast cells are known to play an important role in host defense against several pathogens, but their role in viral infection has not yet been elucidated. The effects of dengue virus infection on the production of chemokines by human mast cells were examined. Elevated levels of secreted RANTES, MIP-1alpha, and MIP-1beta, but not IL-8 or ENA-78, were observed following infection of KU812 or HMC-1 human mast cell-basophil lines. In some cases a >200-fold increase in RANTES production was observed. Cord blood-derived cultured human mast cells treated with dengue virus in the presence of subneutralizing concentrations of dengue virus-specific antibody also demonstrated significantly (P < 0.05) increased RANTES production, under conditions which did not induce significant degranulation. Chemokine responses were not observed when mast cells were treated with UV-inactivated dengue virus in the presence or absence of human dengue virus-specific antibody. Neither antibody-enhanced dengue virus infection of the highly permissive U937 monocytic cell line nor adenovirus infection of mast cells induced a RANTES, MIP-1alpha, or MIP-1beta response, demonstrating a selective mast cell response to dengue virus. These results suggest a role for mast cells in the initiation of chemokine-dependent host responses to dengue virus infection.

Antibodies, Viral↗
PubMed2003

Yellow fever virus/dengue-2 virus and yellow fever virus/dengue-4 virus chimeras: biological characterization, immunogenicity, and protection against dengue encephalitis in the mouse model.

Two yellow fever virus (YFV)/dengue virus chimeras which encode the prM and E proteins of either dengue virus serotype 2 (dengue-2 virus) or dengue-4 virus within the genome of the YFV 17D strain (YF5.2iv infectious clone) were constructed and characterized for their properties in cell culture and as experimental vaccines in mice. The prM and E proteins appeared to be properly processed and glycosylated, and in plaque reduction neutralization tests and other assays of antigenic specificity, the E proteins exhibited profiles which resembled those of the homologous dengue virus serotypes. Both chimeric viruses replicated in cell lines of vertebrate and mosquito origin to levels comparable to those of homologous dengue viruses but less efficiently than the YF5.2iv parent. YFV/dengue-4 virus, but not YFV/dengue-2 virus, was neurovirulent for 3-week-old mice by intracerebral inoculation; however, both viruses were attenuated when administered by the intraperitoneal route in mice of that age. Single-dose inoculation of either chimeric virus at a dose of 10(5) PFU by the intraperitoneal route induced detectable levels of neutralizing antibodies against the homologous dengue virus strains. Mice which had been immunized in this manner were fully protected from challenge with homologous neurovirulent dengue viruses by intracerebral inoculation compared to unimmunized mice. Protection was associated with significant increases in geometric mean titers of neutralizing antibody compared to those for unimmunized mice. These data indicate that YFV/dengue virus chimeras elicit antibodies which represent protective memory responses in the mouse model of dengue encephalitis. The levels of neurovirulence and immunogenicity of the chimeric viruses in mice correlate with the degree of adaptation of the dengue virus strain to mice. This study supports ongoing investigations concerning the use of this technology for development of a live attenuated viral vaccine against dengue viruses.

Amino Acid Sequence↗
PubMed2003

Guidelines on the cost-effectiveness of larval control programs to reduce dengue transmission in Puerto Rico.

OBJECTIVE: In the past 20 years, the emphasis for avoiding dengue epidemics has focused on larval control of Aedes aegypti, the principal mosquito vector of dengue viruses. A general consensus is that mosquito larval control holds the best promise for reducing dengue epidemics, although its actual effectiveness is still unknown and subject to a great deal of uncertainty. The objective of this research was to assess the cost-effectiveness of emergency larval control programs for reducing dengue transmission in the Caribbean island of Puerto Rico and to develop guidelines to help choose between carrying out a rapid-response, emergency larval control intervention and not conducting such an intervention. DESIGN AND METHODS: Data on dengue transmission and its likely impacts in Puerto Rico were used as a case study to develop intervention guidelines. A distribution of economic impacts was simulated using available data on disease rates and economic variables, including the costs of treating patients and the opportunity costs represented by lost wages. Successful larval control interventions were assessed by determining two parameters: (1) the costs of an intervention and (2) the expected reduction in the reported case rate of dengue. In addition, we examined how these guidelines would change with an early warning system that provides information on a possible outbreak of dengue. RESULTS: In Puerto Rico, larval control programs that are expected to reduce dengue transmission by 50% and cost less than US$ 2.50 per person will be cost-effective. Programs that cost more per person but that further reduce transmission are still likely to be cost-effective. Having an early warning system, even one that provides a low level of accuracy, can extend the range of larval control programs that are cost-effective. For example, with an early warning system, a larval control program that reduces dengue transmission by 50% and that costs less than US$ 4.50 per person would be expected to be cost-effective. CONCLUSIONS: Guidelines such as the ones that we developed for Puerto Rico can be useful to public health authorities in helping to decide whether or not to spend resources for a larval control program to reduce dengue transmission. The range of larval control interventions that are cost-effective can be increased by having an early warning system that provides even a small amount of information regarding possible outbreaks.

Aedes↗