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PubMed1985

Genetic relationships of the dengue virus serotypes.

Previous studies have compared RNA genomes from the different dengue virus serotypes by cDNA-RNA hybridization using dengue-1 virus- and dengue-2 virus-specific cDNA probes. These probes revealed that there is a close genetic relationship between dengue virus serotypes 1 and 4. In this communication, the cDNA-RNA hybridization results using dengue-3- and dengue-4-specific cDNA probes to determine the genetic relatedness of all four dengue virus serotypes are reported. The results indicate that serotypes 1 and 4 are genetically very closely related (sharing about 70% of their genomes as detected by both the dengue-1 and dengue-4 cDNA probes), as are serotypes 3 and 4 (sharing about 50% of their genomes as detected by both the dengue-3 and dengue-4 cDNA probes). Serotype 2 does not seem to be very closely related to the other dengue virus serotypes by cDNA-RNA hybridization analysis.

Base Sequence↗
PubMed1996

Dominant recognition by human CD8+ cytotoxic T lymphocytes of dengue virus nonstructural proteins NS3 and NS1.2a.

A severe complication of dengue virus infection, dengue hemorrhagic fever (DHF), is hypothesized to be immunologically mediated and virus-specific cytotoxic T lymphocytes (CTLs) may trigger DHF. It is also likely that dengue virus-specific CTLs are important for recovery from dengue virus infections. There is little available information on the human CD8+ T cell responses to dengue viruses. Memory CD8+CTL responses were analyzed to determine the diversity of the T cell response to dengue virus and to identify immunodominant proteins using PBMC from eight healthy adult volunteers who had received monovalent, live-attenuated candidate vaccines of the four dengue serotypes. All the donors had specific T cell proliferation to dengue and to other flaviviruses that we tested. CTLs were generated from the stimulated PBMC of all donors, and in the seven donors tested, dengue virus-specific CD8+CTL activity was demonstrated. The nonstructural (NS3 and NS1.2a) and envelope (E) proteins were recognized by CD8+CTLs from six, five, and three donors, respectively. All donors recognized either NS3 or NS1.2a. In one donor who received a dengue 4 vaccine, CTL killing was seen in bulk culture against the premembrane protein (prM). This is the first demonstration of a CTL response against the prM protein. The CTL responses using the PBMC of two donors were serotype specific, whereas all other donors had serotype-cross-reactive responses. For one donor, CTLs specific for E, NS1.2a, and NS3 proteins were all HLA-B44 restricted. For three other donors tested, the potential restricting alleles for recognition of NS3 were B38, A24, and/or B62 and B35. These results indicate that the CD8+CTL responses of humans after immunization with one serotype of dengue virus are diverse and directed against a variety of proteins. The NS3 and NS1.2a proteins should be considered when designing subunit vaccines for dengue.

Adult↗
PubMed2006

Dengue as a cause of acute undifferentiated fever in Vietnam.

BACKGROUND: Dengue is a common cause of fever in the tropics but its contribution to the total burden of febrile illnesses that is presented to primary health facilities in endemic regions such as Vietnam, is largely unknown. We aimed to report the frequency of dengue as a cause of fever in Binh Thuan Province, to describe the characteristics of dengue patients, and analyze the diagnostic accuracy of the health care workers and the determinants of the diagnostic process. METHODS: All patients presenting with acute undifferentiated fever at twelve community health posts and one clinic at the provincial malaria station, Binh Thuan Province, a dengue endemic province in southern Vietnam, were included. Record forms were used to fill in patient and diseases characteristics, pre-referral treatment, signs and symptoms, provisional diagnosis and prescribed treatment, referral and final outcome. Serum samples were collected at first presentation and after 3 weeks for serologic diagnosis. RESULTS: 2096 patients were included from April 2001 to March 2002. All 697 patients with paired serum samples were tested for dengue virus IgM and IgG. Acute dengue was found in 33.6% cases and past dengue virus infections were found in 57.1% cases. Acute primary infections were more common among children under 15 years old than among adults (7.7% vs. 3.5%, p value < 0.001). Younger age significantly predicted acute dengue (RR per increasing year of age (95 % CI): 0.986 (0.975-0.997, p value = 0.014). 48.9% of cases with clinical diagnosis of acute dengue were serologically confirmed and 32.5% of cases without clinical diagnosis of acute dengue were positive by serology after all (OR = 1.981, p value 0.025, 95% CI: 1.079-3.635). Tourniquet test was not a predictor for dengue diagnosis. CONCLUSION: Dengue is responsible for one third of the fevers presented to the public primary health services in Binh Thuan, southern Vietnam. It presents as a highly unspecific illness and is hardly recognized as a clinical entity by primary physicians.

Adolescent↗
PubMed1998

Using disability-adjusted life years to assess the economic impact of dengue in Puerto Rico: 1984-1994.

This study presents the disability-adjusted life years (DALYs), a non-monetary economic measure of impact, lost to dengue in Puerto Rico for the period 1984-1994. Data on the number of reported cases, cases with hemorrhagic manifestations, hospitalizations, and deaths were obtained from a surveillance system maintained at the Dengue Branch, Division of Vector-Borne Infectious Diseases, Centers for Disease Control and Prevention (San Juan, PR). The reported cases were divided into two age groups (0-15 years old and >15 years old), and then multiplied by predetermined factors (10 for 0-15 years; 27 for >15 years) to allow for age-related under-reporting of cases. Severity of dengue was modeled by classifying cases into three groups: dengue fever, dengue with severe manifestations, and hospitalized cases. Each group was assigned a different number of days lost because of dengue-related disability. Dengue caused an average of 658 DALYs per year per million population (SE = 114, range = 145-1,519). A multivariate sensitivity analysis, which simultaneously altered the values of six input variables, produced a mean of 580 DALYs/year/million population, with a maximum average of 1,021 DALYs/year/million population, and a maximum, single-year estimate for 1994 of 2,153 DALYs/million population. The most important input was the number of days lost to classic dengue. The DALYs/year/million population lost to dengue in Puerto Rico are much greater than previous estimates concerning the impact of dengue hemorrhagic fever alone. The loss to dengue is similar to the losses per million population in the Latin American and Caribbean region attributed to any of the following diseases or disease clusters; the childhood cluster (polio, measles, pertussis, diphtheria, tetanus), meningitis, hepatitis, or malaria. The loss is also of the same order of magnitude as any one of the following: tuberculosis, sexually transmitted diseases (excluding human immunodeficiency virus), tropical cluster (e.g., Chagas' disease, leishmaniasis), or intestinal helminths. The results objectively suggest that when governments and international funding agencies allocate resources for research and control, dengue should be given a priority equal to many other infectious diseases that are generally considered more important.

Adolescent↗
PubMed2001

Neurological manifestations in dengue patients.

To determine the frequency and the natural history of neurological manifestations of dengue infection in Thai children, 1,493 children diagnosed with dengue infection by serology and admitted to the Department of Pediatrics, Chulalongkorn Hospital, Bangkok, Thailand from 1987 to 1998 were reviewed from prospectively recorded medical charts. There were 80 children identified with neurological manifestations, an incidence of 5.4% of all dengue patients. Of these, there were 41 males and 39 females, with ages ranging from 3 months to 14 years. They were categorized into 20 cases of dengue fever, 26 cases of dengue hemorrhagic fever and 34 cases of dengue shock syndrome. All cases experienced the neurological manifestations during the febrile stage of the illness. The patients were classified into an encephalitic group (called "dengue encephalopathy") (42), a seizure group (35) and a miscellaneous group (3). Encephalitic patients presented with alteration of consciousness (83.3%), seizure (45.2%), mental confusion (23.8%), nuchal rigidity (21.4%), spasticity of limbs (9.5%), positive clonus (4.8%), hemiplegia (2.4%) and positive kernig (2.4%), and were older than those in the other groups. Patients in the seizure group presented with seizure (100%) and positive clonus (2.9%). Abnormal laboratory findings included hyponatremia, abnormal liver enzymes and CSF pleocytosis. Dengue IgM and dengue PCR were not demonstrated in 16 CSF specimens. An autopsy finding of a child in the encephalitic group showed histologic evidence of encephalitis, the only case of confirmed dengue encephalitis in this study. One patient with encephalitic symptoms suffered from long-term neurological sequelae. The overall mortality rate was 5%. In conclusion, neurological manifestations including seizure and encephalopathy in children with dengue are not uncommon whereas dengue encephalitis is a rare entity.

Adolescent↗
PubMed2004

Seroprevalence of dengu infections amongst the children.

Serosurvillance of 650 children of clinically suspected dengue infection based on simple laboratory tests were evaluated to find out the early indicator for diagnosis of dengue infection. The study was conducted among the patients attending the Sir Salimullah Medical College (SSMC) and Mitford Hospital and Popular Diagnostic Center, Dhaka, during July 2002 to September 2002. Of these 650 suspected dengue cases, 294 were in the age group 1-5 years, 206 were in age group 6-10 years and 150 cases in age group 11-15 years, of which Seropositivity was found in 78 (26.53%), 60 (24.12%) and 65 (43.33%) cases respectively. Primary dengue IgM was positive in 123 (60.59%) cases and secondary dengue (IgG & IgM combined or IgG alone) was positive in 80 (39.41%) cases. Leucopenia was found in 90 (75%) cases and Thrombocytopenia was found in 95 (79.16%) cases in primary dengue cases. Similarly in secondary dengue cases TWBC and PLT was decreased in 60 (72.29%) and 65 (78.15%) cases respectively. Haemoconcentration was found in 40 (36.67%) cases of primary dengue and 13 (18%) cases in secondary dengue. Month wise distribution of dengue seropositivity shows that 10 (8.53%) cases was found in July, 175 (50.10%) cases in August and 78 (10.00%) cases in September. This study reveals that seropositivity is highest (43.33%), in the age group 11-15 years and incidence of dengue increased in the month of August. Leucopenia (WBC <or= 5000) and Thrombocytopenia (Patelet count <or= 100000) were two findings that help in the early diagnosis of dengue infection.

Adolescent↗
PubMed2006

Travel-associated dengue--United States, 2005.

Dengue is a mosquito-transmitted, acute viral disease caused by any of four dengue virus serotypes (DEN-1, DEN-2, DEN-3, or DEN-4). Dengue is endemic in most tropical and subtropical areas of the world and has occurred among U.S. residents returning from travel to such areas. In collaboration with state health departments, CDC maintains a passive surveillance system for travel-associated dengue among U.S. residents. Suspected dengue in travelers is reported to state health departments, which forward specimens to CDC for diagnostic testing. A case of travel-associated dengue is defined as laboratory-diagnosed dengue in a resident of one of the 50 states or the District of Columbia (DC) who traveled to a dengue-endemic area outside the United States or DC any time during the 14 days before symptom onset. This report summarizes information regarding 96 travel-associated dengue cases, including one fatality, among U.S. residents during 2005. Travelers to tropical areas can reduce their risk for dengue by using mosquito repellent and avoiding exposure to mosquitoes. Health-care providers should consider dengue in the differential diagnosis of febrile illness in patients who have returned recently from dengue-endemic areas.

Adolescent↗
PubMed1989

[A preliminary report of the fetal effects of dengue infection in pregnancy].

This Manuscript was read at the Clinical Aspects on Dengue Fever and Dengue Hemorrhagic Fever held at Kaohsiung Medical College, Kaohsiung City, Taiwan, Republic of China, November 13, 1988. There is not enough evidence to prove that the dengue virus will cause teratogenicity, abortion, or intrauterine growth retardation of a fetus during pregnancy. Nine cases of women infected with dengue fever in early pregnancy received amniocentesis (or chorion villi sampling) in the Department of Obstetrics and Gynecology, KMCH. The chromosome analysis revealed that all were normal, and the level of alpha-fetoprotein in amniotic fluids and maternal sera were within normal range. Antibodies to the dengue virus in the dengue infected mother can cross the placenta and transfer to the fetus, which can cause new born infants to develop dengue hemorrhagic fever or dengue shock syndrome easily when they are primarily infected with dengue virus. Anti-dengue activity was found in the lipid component of human milk and colostrum. This suggests that breast feeding will protect the infant from the dengue virus in the endemic area of dengue infection.

Abortion, Spontaneous↗
PubMed2000

Neurological manifestations of dengue infection.

BACKGROUND: Severe forms of dengue, the most important arboviral infection of man, are associated with haemorrhagic disease and a generalised vascular leak syndrome. The importance of dengue as a cause of neurological disease is uncertain. METHODS: During 1995, all patients with suspected CNS infections admitted to a referral hospital in southern Vietnam were investigated by culture, PCR, and antibody measurement in serum and CSF for dengue and other viruses. FINDINGS: Of 378 patients, 16 (4.2%) were infected with dengue viruses, compared with four (1.4%) of 286 hospital controls (odds ratio [95% CI] 3.1 [1.7-5.8]). Five additional dengue positive patients with CNS abnormalities were studied subsequently. No other cause of CNS infection was identified. Seven infections were primary dengue, 13 secondary, and one was not classified. Ten patients had dengue viruses isolated or detected by PCR, and three had dengue antibody in the CSF. 12 of the 21 had no characteristic features of dengue on admission. The most frequent neurological manifestations were reduced consciousness and convulsions. Nine patients had encephalitis. No patient died, but six had neurological sequelae at discharge. Phylogenetic analysis of the four DEN-2 strains isolated mapped them with a DEN-2 strain isolated from a patient with dengue haemorrhagic fever, and with other strains previously isolated in southern Vietnam. INTERPRETATION: In dengue endemic areas patients with encephalitis and encephalopathy should be investigated for this infection, whether or not they have other features of the disease.

Adolescent↗
PubMed2006

Slower rates of clearance of viral load and virus-containing immune complexes in patients with dengue hemorrhagic fever.

BACKGROUND: Although previous studies have revealed the contribution of an initial high level of dengue virus replication to the severe and potentially life-threatening diseases dengue hemorrhagic fever (DHF) and dengue shock syndrome, the involvement of dengue virus in the immunopathological processes during the transition from fever to defervescence, which is a critical stage in determining the progression to DHF, has not been appreciated. Previously, we reported that dengue virus can be detected in the immune complexes of patients with DHF during this period. METHODS: We investigated plasma dengue viral load, virus in immune complexes, antibody response, complements, and cytokines for 54 patients with dengue fever (a relatively mild form of disease) and 49 patients with DHF. The patients had confirmed secondary infection with dengue virus type 2 from a large outbreak in southern Taiwan in 2002. RESULTS: Patients with DHF had a significantly higher viral load and a slower rate of clearance than patients with dengue fever. For viral loads >5.7 log RNA copies/mL on the day of defervescence, the positive and negative predictive values for DHF are 0.88 and 0.95, respectively. A higher level and slower decline of dengue virus-containing immune complexes (and a subsequently higher elevation of C5a and soluble interleukin 2 receptor) were found in patients with DHF, compared with patients with dengue fever. CONCLUSIONS: These findings indicate that slower rates of clearance of viral load and virus-containing immune complexes are associated with subsequent immune activation and contribute to the progression of DHF at this critical stage. Moreover, viral load on the day of defervescence can predict cases of DHF.

Adolescent↗
PubMed2006

Two complex, adenovirus-based vaccines that together induce immune responses to all four dengue virus serotypes.

Dengue virus infections can cause hemorrhagic fever, shock, encephalitis, and even death. Worldwide, approximately 2.5 billion people live in dengue-infested regions with about 100 million new cases each year, although many of these infections are believed to be silent. There are four antigenically distinct serotypes of dengue virus; thus, immunity from one serotype will not cross-protect from infection with the other three. The difficulties that hamper vaccine development include requirements of the natural conformation of the envelope glycoprotein to induce neutralizing immune responses and the necessity of presenting antigens of all four serotypes. Currently, the only way to meet these requirements is to use a mixture of four serotypes of live attenuated dengue viruses, but safety remains a major problem. In this study, we have developed the basis for a tetravalent dengue vaccine using a novel complex adenovirus platform that is capable of expressing multiple antigens de novo. This dengue vaccine is constructed as a pair of vectors that each expresses the premembrane and envelope genes of two different dengue virus serotypes. Upon vaccination, the vaccine expressed high levels of the dengue virus antigens in cells to mimic a natural infection and induced both humoral and cellular immune responses against multiple serotypes of dengue virus in an animal model. Further analyses show the humoral responses were indeed neutralizing against all four serotypes. Our studies demonstrate the concept of mimicking infections to induce immune responses by synthesizing dengue virus membrane antigens de novo and the feasibility of developing an effective tetravalent dengue vaccine by vector-mediated expression of glycoproteins of the four serotypes.

Adenoviridae↗
PubMed2000

[Stratification of a hyperendemic city in hemorrhagic dengue].

Any effort to control dengue hemorrhagic fever (DHF) faces a number of challenges. Among these are the great environmental heterogeneity of homes and neighborhoods in urban centers where the primary dengue vector, Aedes aegypti, breeds, as well as shortages of resources and of personnel trained in mosquito control. Adequate epidemiological surveillance could serve as a basis to begin to stratify urban communities and identify the areas in them where control efforts should be focused. In this study we stratified Maracay, Venezuela, a city with hyperendemic dengue hemorrhagic fever, using a geographic information system and analyzing the persistence, incidence, and prevalence of dengue, by means of clinical diagnoses reported from 1993 through 1998. Maracay has around one million inhabitants living in some 349 neighborhoods in the six communities that make up the greater Maracay metropolitan area. During that 1993-1998 period the Maracay area reported 10,576 cases of dengue, 2,593 cases of DHF, and 8 deaths. The incidence of DHF was related to the incidence of dengue, the number of inhabitants in an area, and population density. The spatial pattern of dengue incidence was stable over the years that were studied, and significant, positive relationships were found between pairs of years and the incidence of dengue by neighborhood. The persistence of dengue was related directly to monthly incidence by neighborhood. These spatial patterns helped to divide the city into three strata: 68 neighborhoods without apparent dengue, 226 neighborhoods with low persistence and prevalence, and 55 neighborhoods with high persistence and prevalence. We recommend giving the highest priority for control efforts to these 55 neighborhoods, which make up just 35% of the Maracay urban area but had 70% of all the reported dengue cases.

Aedes↗
PubMed2002

Transient CD4/CD8 ratio inversion and aberrant immune activation during dengue virus infection.

The immune status after dengue virus infection was studied in dengue patients from an outbreak of serotype 3 dengue virus infection in the southern part of Taiwan during November and December 1998. Consecutive blood samples from 29 dengue patients, of whom 21 had dengue fever and 8 had dengue hemorrhagic fever/dengue shock syndrome, were collected, and the immunophenotypes of the peripheral blood mononuclear cells were determined by flow cytometry. The early activation marker CD69 appeared on lymphocytes and monocytes at day 4 after the onset of fever, and declined afterward. However, a transient reverse in the CD4/CD8 ratio occurred at days 6-10 after the onset of fever. The CD4/CD8 ratio inversion was manifested in 10 of 29 dengue patients and was encountered more frequently in dengue hemorrhagic fever/dengue shock syndrome than in dengue fever patients. Analysis of the clinical blood cell count of these 10 cases showed that increase of immature neutrophils developed at fever days 5-6, CD4(dim) or CD8(dim) monocytosis at days 6-7, and atypical lymphocytosis at days 8-10 after the onset of fever. Serum IL-6 was found at either day 7 or day 9-11. The PHA-stimulated T-cell response was depressed as well. These changes in immune parameters indicate aberrant immune activation during dengue virus infection and might be involved in the pathogenesis of dengue virus infection.

Antigens, CD↗
PubMed1992

Dengue virus infection of human skin fibroblasts in vitro production of IFN-beta, IL-6 and GM-CSF.

Dengue virus is transmitted to humans by the bite of infected mosquitos. In our efforts to understand the pathogenesis of dengue virus infection, we examined whether skin fibroblasts can be infected in vitro with dengue viruses. Fibroblasts could be infected with dengue viruses, yellow fever virus and West Nile virus. Dengue virus antigen-positive cells were detected as early as 4 h and the percentage of dengue virus antigen-positive cells reached maximum levels by 24 h after infection. High titers of infectious dengue virus were also detected in the culture supernatants at 20 h after infection. Dengue virus-infected fibroblasts produced interferon-beta (IFN-beta), and the IFN-beta protected uninfected fibroblasts from dengue virus infection. Dengue virus-infected fibroblasts also produced interleukin 6 (IL-6) and granulocyte macrophage colony stimulation factor (GM-CSF). These results suggest that skin fibroblasts may be one of the cell types which first support dengue virus and other flavivirus infections in vivo after introduction by the bite of infected mosquito, and that production of IFN-beta, IL-6, and GM-CSF by these virus-infected fibroblasts may be important host immune responses to control flavivirus infections.

Cells, Cultured↗
PubMed2001

Development of a fluorogenic RT-PCR system for quantitative identification of dengue virus serotypes 1-4 using conserved and serotype-specific 3' noncoding sequences.

A fluorogenic reverse transcriptase-polymerase chain reaction (RT-PCR) system was developed for use as a rapid diagnostic test for determining dengue viremia. The dengue virus 3'-noncoding sequence was utilized to formulate serotype-specific RT-PCR assays for quantitative identification of the four different dengue virus serotypes. A generic RT primer set containing two dengue specific anti-sense primers (DV-L1 and DV-L2) could be used to transcribe extracted viral RNA of all four dengue virus types to complimentary DNA (cDNA). The resultant dengue viral cDNA could be quantitatively identified at the serotype level by the 5'-3' exonuclease assay using four serotype-specific sense primers. The fluorogenic dengue type-specific RT-PCR can detect each of the four dengue types at similar low detection limits, i.e. 20-50 plaque forming units per milliliter of serum. Two panels with four dengue reference serotypes and 134 clinical samples were used to validate detection sensitivity and specificity of the dengue serotype RT-PCR assay, using virus isolation in cell culture as the criterion standard. By analyzing sera samples from Puerto Rico that were collected from 1999 through 2000, the assay demonstrated high level detection sensitivity and specificity of 92.8 and 92.4%, respectively, for all four dengue virus serotypes.

3' Untranslated Regions↗
PubMed2002

Comparison of four reverse transcription-polymerase chain reaction procedures for the detection of dengue virus in clinical specimens.

The sensitivity of dengue virus identification by mosquito inoculation and four reverse transcription-polymerase chain reaction (RT-PCR) procedures (Am. J. Trop. Med. Hyg. 45 (1991) 418 (H); J. Clin. Microbiol. 29 (1991) 2107 (M); J. Clin. Microbiol. 30 (1992) 545 (L); and Southeast Asian J. Trop. Med. Public Health 27 (1996) 228 (Y)) were compared using coded clinical specimens derived from areas in Thailand where all four dengue serotypes circulate. The sensitivity of virus detection in serologically confirmed dengue cases was 54, 52, 60, 79, and 80% for mosquito inoculation, procedures H, M, L and Y, respectively. In comparison to clinical specimens which yielded virus isolates by mosquito inoculation, there was relatively low sensitivity in detecting each of the four dengue serotypes by PCR: procedure H-dengue 4 (25%), procedure M-dengue 3 (73%), procedure L-dengue 1 (70%), and procedure Y-dengue 1 (79%). Dengue virus was detectable by RT-PCR for more days of illness and in the presence of dengue-specific antibody when compared to virus isolated in mosquitoes. Procedures L and Y were more sensitive than mosquito inoculation or procedures H and M in detecting all four dengue serotypes in clinical specimens and may be the RT-PCR methods of choice for virus surveillance or research use.

Aedes↗
PubMed2000

Quantitative detection of dengue 2 virus using fluorogenic RT-PCR based on 3'-noncoding sequence.

A fluorescent DNA probe (DV2.P1) specific to the conserved distal 3'-noncoding region (nucleotides 10653-10678) of dengue 2 virus and a pair of flanking primers (DV2.L1 and DV2.U2) were designed to formulate a dengue 2-specific fluorogenic polymerase chain reaction (PCR). In addition, DV2.L1 was also used as a reverse transcription (RT) primer to generate superior cDNA from dengue viral RNA. Optimal assay conditions with zero background were established to detect low levels of dengue 2 virus from clinical specimens. The range of dengue virus detection in spiked human sera was determined to be from 10 to 10(6) infectious virions per milliliter (plaque forming units determined using Vero cell line). Dengue 2 virus isolates from different geographic regions can be detected universally and identified by the fluorogenic RT-PCR assay. Moreover, the assay is specific for dengue 2 virus and does not recognize other related flaviviruses, including dengue serotypes 1, 3 and 4, Japanese encephalitis, St. Louis encephalitis, yellow fever, and Kunjin viruses. The assay also detected efficiently immunocomplexed dengue viruses. In practice, the fluorogenic RT-PCR assay detected readily viremia in sera collected from individuals ill with dengue fever. The rise and fall of dengue 2 virus concentrations in rhesus monkeys, reflecting viral proliferation and clearance, was also clearly illustrated by the assay.

3' Untranslated Regions↗
PubMed2005

Cross-serotype neutralization of dengue virus in Aotus nancymae monkeys.

Previously, we observed that serum from humans immune to dengue serotype 1 (dengue-1) neutralized the American genotype of dengue serotype 2 (American-2) to a greater extent than it neutralized the Asian genotype of dengue serotype 2 (Asian-2). To determine if this activity is protective, Aotus nancymae monkeys were infected with dengue-1 followed by either American-2 or Asian-2. Dengue-1-infected animals produced antibody with neutralizing titers of 2656 antibodies against dengue-1, 409 against American-2, and <20 against Asian-2. Infection with American-2 did not produce detectable viremia in either dengue-1-immune or dengue-1-naive animals. These findings support the hypothesis that dengue-1 immunity might have prevented disease or altered the severity of disease in individuals sequentially infected with dengue-1 and American-2.

Animals↗