Asymptomatic Dengue Research Articles

Association of IL-10 gene polymorphism with the susceptibility to dengue and disease severity in a population with asymptomatic and symptomatic dengue.

Infections caused by Orthoflavivirus denguei can either manifest asymptomatically or present a wide spectrum of clinical manifestations. This variety of symptoms results from its complex pathogenesis, which is influenced by viral factors, in addition to host genetics and immunological factors. It is known that anti-inflammatory cytokines can play an immunomodulatory role throughout the course of dengue. Therefore, we investigated the single nucleotide polymorphisms (SNPs) -1082 A/G (rs1800896) and -819 C/T (rs1800871) in the interleukin-10 (IL-10) gene and their possible relationship with the development of symptomatic dengue in a Brazilian population. This study, carried out in northeastern Brazil, involved 333 volunteers, including 74 patients with dengue without warning signs (DWWS), 45 patients with dengue with warning signs (DWAS), 85 patients with asymptomatic dengue infection (ASY) and 129 health controls. The genomic DNA was extracted and the SNPs were genotyped using quantitative real-time polymerase chain reaction (qPCR). The data obtained were used to conduct statistical analyses of the genotype and allele frequencies. We observed an association of A/G and G/G genotypes of the -1082 A/G SNP of the IL-10 gene with susceptibility to symptomatic dengue and DWAS regarding the asymptomatic dengue. The G allele of this SNP has also been identified as a risk factor for symptomatic dengue, DWWS and DWAS. Regarding the analyses between the SNPs -1082 A/G and -819 C/T of the IL-10 gene, there was an association of the G-C haplotype with symptomatic dengue, DWWS and DWAS, as well as a correlation of the A-C haplotype with asymptomatic dengue. Moreover, the data indicate an association between the presence of the G allele and the development of symptoms, compared to those without the G allele. Our results indicate the presence of the G allele of SNP -1082 A/G of the IL-10 gene as a risk factor for the clinical development of symptomatic dengue in the studied population and show the importance of genomics association studies involving asymptomatic individuals.

Estimating dengue burden among family contacts through cluster investigation around probable cases in 2022 and 2023 in the Central Region, Burkina Faso

BackgroundIn 2023, Burkina Faso experienced the largest dengue epidemic ever in Africa. This study aimed to estimate the prevalence of symptomatic, subclinical, and asymptomatic dengue and determine the associated factors among adult contacts of dengue in the Central Region, Burkina Faso.MethodsThis cross-sectional study included contacts of dengue probable cases through cluster sampling in 2022–2023. These suspected cases that tested positive were identified from the five health facilities (Pissy CMA, Saaba CM, Kossodo CMA, Samandin CM, and Marcoussis CSPS) that reported the highest number of cases in 2021 per district. All participants underwent dengue and malaria rapid diagnostic tests (RDT). Samples positive for non-structural 1 protein antigen (AgNS1) and/or immunoglobulin M (IgM) were tested for serotype detection by reverse transcription polymerase chain reaction (RT-PCR). Binary logistic regression was done to identify the determinants of asymptomatic, subclinical, and symptomatic dengue among contacts of probable dengue cases.ResultsA total of 484 contacts were included, mostly in 2023 (75.2%). Most participants were females (58.6%), residing (24.3%) and passing their daytime (23.1%) in Saaba. The overall prevalence of dengue was estimated at 15.1% [95% confidence interval (CI): 12.0–18.6%], representing cases not seeking care in hospitals. Asymptomatic cases represented 2.9% (95% CI: 1.6–4.8%). Subclinical and symptomatic cases accounted for 6.0% (95% CI: 4.1–8.5%) and 6.2% (95% CI: 4.2–8.7%), respectively. Of the 58 samples tested by RT-PCR, 10 were confirmed for serotype 3 in 2023. Malaria cases were estimated at 5.6% (95% CI: 3.7–8.0%). After adjustment, participants claiming that a virus transmits dengue were likelier to have asymptomatic dengue [adjusted odds ratio (aOR) = 7.1, 95% CI: 2.4–21.0]. From the multivariable analysis, subclinical dengue was statistically associated with being included in the study in 2023 (aOR = 30.2, 95% CI: 2.0–455.5) and spending the daytime at Arrondissement 4 (aOR = 11.5, 95% CI: 1.0–131.0). After adjustment, symptomatic dengue was associated with living less than 50 m away from cultivated land (aOR = 2.8, 95% CI: 1.1–6.9) and living less than 50 m from a stretch of water (aOR = 0.1, 95% CI: 0.0–0.6).ConclusionsThe overall burden of dengue among populations not seeking care in hospitals was quite high, with few asymptomatic cases. Efforts to manage dengue cases should also target non-hospital cases and raise population awareness. The 2023 epidemic could be due to dengue virus (DENV)-3.Graphical

Low Rate of Asymptomatic Dengue Infection Detected in Coastal Kenya Using Pooled Polymerase Chain Reaction Testing.

Asymptomatic dengue virus (DENV) infections have important public health implications but are challenging to identify. We performed a cross-sectional study of reverse transcription quantitative polymerase chain reaction on pooled sera of asymptomatic individuals from the south coast of Kenya at two time periods to identify cases of asymptomatic viremia. Among 2,460 samples tested in pools of 9 or 10, we found only one positive case (0.04% incidence). Although pooling of samples has the potential to be a cost-effective and time-efficient method for asymptomatic DENV detection, mass cross-sectional pooled testing may not provide accurate data on rates of asymptomatic infection, likely owing to a decrease in the sensitivity with pooling of samples, a short period of viremia, or testing in the absence of an outbreak.

Association of Vitamin D with Biochemical Severity Markers in Dengue Patients

Background: Dengue fever is a common virus that has rapidly spread to all parts of the world. Dengue causes two critical disease dengue shock syndrome and dengue hemorrhagic fever. Aim: To determine whether vitamin D levels and the severity of dengue are linked in any way. Study design: Cohort study Place and duration of study: Department of Medicine, Fauji Foundation Hospital Rawalpindi from 15-08-2022 to 15-11-2022. Methodology: The patient's sample was collected to monitor the complete blood picture, including total leukocyte count and hemoglobin, hematocrit, platelets, etc. The severity of dengue was assessed by looking at platelet counts and hematocrit. Results: The mean age was 29.19±16.80 years. There were 51% females and 49% males in the study. Vitamin D levels and platelet levels were weakly correlated with each other (rs= -.408, p= .000). There was a strong, negative correlation between Hb and Vitamin D levels, which was statistically significant (rs= -.704, p= .000). Similarly, hematocrit and highest MCHC also had a strong inverse significant correlation with Vitamin D level (rs= .698, p = .000 and rs= .751, p= .000, respectively). Surprisingly, there were significantly higher vitamin D levels in severe dengue patients than in non-severe ones (p<0.01). Conclusion: Vitamin D levels were higher in severe dengue cases compared to less severe ones, indicating a possible role of vitamin D as a cofactor for predicting disease severity. It is suggested that maintaining an ideal vitamin D level can help avoid the progression of asymptomatic dengue to dengue hemorrhagic fever or dengue shock syndrome. Keywords: Vitamin D, Biochemical severity markers, Dengue

Serological Evidence of Zika virus Circulation with Dengue and Chikungunya Infections in Sri Lanka from 2017.

Arbovirus diseases remain a public health threat in Sri Lanka. Dengue is endemic and two outbreaks of chikungunya infections have been reported. There is limited data on Zika virus (ZIKV) infections in Sri Lanka, and this could be due to a lack of comprehensive ZIKV surveillance. Our aim was to determine the presence of antibodies to dengue, chikungunya, and Zika infections in adults from a suburban population in Sri Lanka. A total of 149 healthy adult volunteers over 18 years of age (mean age: 43±14 years, males - 43%), with no prior diagnosed arboviral infections and no history of overseas travel, participated in the study. ELISA and neutralization assays were carried out to detect past dengue, chikungunya, or Zika infections. A total of 94.6% (141/149) of the participants demonstrated dengue IgG antibodies, 37.5% (56/149) were positive for chikungunya IgG, and 5.3% (8/149) were positive for anti-ZIKV IgG antibodies. Neutralization assays confirmed ZIKV-specific antibodies in 6.7% (10/149), when 40/149 of the participating population were tested. This clearly demonstrated past ZIKV infections in this population. In addition, this study indicates that >90% of individuals had asymptomatic dengue but no serious symptoms. These results provide a cross-sectional view on the DENV, ZIKV, and CHIKV epidemic status and demonstrate a need for the implementation of enhanced surveillance and more effective measures against the spread of these arbovirus diseases.

Temporal patterns of functional anti-dengue antibodies in dengue infected individuals with different disease outcome or infection history

Heterotypic secondary dengue virus (DENV) infection is a risk factor for the development of severe disease. To assess the contribution of the developing polyclonal humoral immune response to the course of acute infection, we have determined anti-DENV IgG titers, neutralizing antibodies, percentages of antibodies binding to DENV-infected cells and antibody‑dependent enhancement (ADE) to the infecting serotype in DENV-infected Cambodian children (n = 58), ranging from asymptomatic dengue to severe disease. The results showed that ADE titers are highest against the infecting serotype during heterotypic secondary DENV-2 infection. Moreover, IgG titers, neutralizing antibodies and ADE titers against the infecting serotype peak at D10 and are maintained until D60 after laboratory-confirmed secondary DENV infection. Anti-DENV IgG titers and the magnitude of the functional antibody response were higher in secondary DENV-infected patients compared to primary infected patients. No differences in antibody titers, neutralizing or enhancing antibodies could be observed between asymptomatic or hospitalized patients between 6 and 8 days after laboratory-confirmed DENV-1 infection. However, at this time point, the level of IgG bound to DENV-infected cells was associated with disease severity in hospitalized patients. Taken together, our data offer insights for more comprehensive interpretation of antibody response profile to natural infection and its correlation to disease outcome.

Incidence of dengue illness in Mexican people aged 6 months to 50 years old: A prospective cohort study conducted in Jalisco.

The burden of dengue virus (DENV), a mosquito-borne pathogen, remains difficult to assess due to misdiagnosis and underreporting. Moreover, the large proportion of asymptomatic dengue cases impairs comprehensive assessment of its epidemiology even where effective surveillance systems are in place. We conducted a prospective community-based study to assess the incidence of symptomatic dengue cases in Zapopan and neighboring municipalities in the state of Jalisco, Mexico. Healthy subjects aged 6 months to 50 years living in households located in the Zapopan and neighboring municipalities were enrolled for a 24-month follow-up study (NCT02766088). Serostatus was determined at enrolment and weekly contacts were conducted via phone calls and home visits. Participants had to report any febrile episode lasting for at least two days. Suspected dengue cases were tested by reverse-transcriptase quantitative polymerase chain reaction (RT-qPCR), detection of non-structural protein 1 (NS1), anti-DENV immunoglobulin G and M (IgG and IgM) assays. A total of 350 individuals from 87 households were enrolled. The overall seroprevalence of anti-DENV IgG at enrolment was 19.4% (95% confidence interval [CI] 14.5-25.6) with the highest seroprevalence rate observed in the adult group. Over the 27-month study period from July 2016 to September 2018, a total of 18 suspected dengue cases were reported. Four cases were confirmed by RT-qPCR and serotyped as DENV-1. A fifth case was confirmed by the NS1 assay. The 13 remaining suspected cases were tested negative by these assays. Based on the 5 virologically confirmed cases, symptomatic dengue incidence proportion of 1.4% (95%CI 0.5-3.8) was estimated. No severe cases or hospitalizations occurred during the study. Community-based active surveillance was shown as efficient to detect symptomatic dengue cases. NCT02766088.

Inapparent dengue in a community living among dengue-positive Aedes mosquitoes and in a hospital in Klang Valley, Malaysia

The public health burden of dengue is most likely under reported. Current dengue control measures only considered symptomatic dengue transmission. Hence, there is a paucity of information on the epidemiology of inapparent dengue. This study reports that many people have been unknowingly exposed to dengue infection. Almost 10% and 70% of individuals without any history of dengue infection and living in a dengue hotspot, in Selangor, Malaysia, were dengue IgM and IgG positive respectively. When dengue-positive mosquitoes were detected in the hotspot, 11 (6.3%) of the 174 individuals tested were found to have dengue viremia, of which 10 were asymptomatic. Besides, upon detection of a dengue-infected mosquito, transmission was already widespread. In a clinical setting, it appears that people living with dengue patients have been exposed to dengue, whether asymptomatic or symptomatic. They can either have circulating viral RNA and/or presence of NS1 antigen. It is also possible that they are dengue seropositive. Collectively, the results indicate that actions taken to control dengue transmission after the first report of dengue cases may be already too late. The current study also revealed challenges in diagnosing clinically inapparent dengue in hyperendemic settings. There is no one best method for diagnosing inapparent dengue. This study demonstrates empirical evidence of inapparent dengue in different settings. Early dengue surveillance in the mosquito population and active serological/virological surveillance in humans can go hand in hand. More studies are required to investigate the epidemiology, seroprevalence, diagnostics, and control of inapparent dengue. It is also crucial to educate the public, health staff and medical professionals on asymptomatic dengue and to propagate awareness, which is important for controlling transmission.

Differential Pattern of Soluble Immune Markers in Asymptomatic Dengue, West Nile and Zika Virus Infections

Infections with dengue virus (DENV), West Nile virus (WNV) and Zika virus (ZIKV) usually present similar mild symptoms at early stages, and most infections (~80%) are asymptomatic. However, these infections may progress to severe disease with different clinical manifestations. In this study we attempted to identify unique characteristics for each infection at the presymptomatic/asymptomatic stage of infection and compared levels of soluble immune markers that have been shown to be altered during clinical course of these viral infections. Levels of soluble markers were determined by Luminex-based assays or by ELISA in plasma samples from asymptomatic blood donors who were reactive for RNA from DENV (n = 71), WNV (n = 52) or ZIKV (n = 44), and a control or non-infected (NI) group (n = 22). Results showed that even in the absence of symptoms, increased interleukin (IL) levels of IL-12, IL-17, IL-10, IL-5, CXCL9, E-Selectin and ST2/IL-1R4; and decreased levels of IL-13 and CD40 were found in all flavivirus group samples, compared to those from NI donors. DENV-infected donors demonstrated variation in expression of IL-1ra and IL-2; WNV-infected donors demonstrated variation in expression of IL-1ra, P-Selectin, IL-4 and IL-5; ZIKV-infected donors demonstrated variation in expression of IL-1ra, P-Selectin, IL-4, RANK-L, CD40L and C3a. The findings suggest that, even in the presymptomatic/asymptomatic phase of the infection, different immunomodulation profiles were associated with DENV, WNV and ZIKV infections.

Seroprevalence of Asymptomatic Dengue Virus Infection and Its Antibodies Among Healthy/Eligible Saudi Blood Donors: Findings From Holy Makkah City.

BACKGROUNDThreat to blood transfusion–transmitted dengue virus (DENV) and its antibodies has recently emerged worldwide. Dengue fever is an endemic disease in Saudi Arabia, particularly in its Western region. The aim of this study was to estimate the seroprevalence of asymptomatic DENV infection and its antibodies among eligible Saudi blood donors.METHODSSerum samples from 910 healthy/eligible adult male Saudi blood donors, who reside in Holy Makkah City of Saudi Arabia, were collected between March 2015 and August 2016 and screened for the detection of DENV nonstructural protein 1 (NS1) antigen and anti-DENV IgM and IgG antibodies using commercial enzyme-linked immunosorbent assay kits (Panbio, Brisbane, QLD, Australia).RESULTSAmong the tested donors, 48 (5.3%) were seropositive for DENV-NS1 antigen, whereas 50 (5.5%) and 354 (38.9%) were seropositive for anti-DENV IgM and IgG antibodies, respectively. Seropositivity for DENV-NS1 antigen and/or anti-DENV IgM antibody among the tested donors reflects their ongoing asymptomatic viremic infectious stage with DENV during their donation time, whereas high prevalence of anti-DENV IgG seropositivity reflects the high endemicity of dengue disease in this region of Saudi Arabia.CONCLUSIONSThese results show high prevalence of asymptomatic DENV infection and its antibodies among Saudi blood donors, raising the importance of establishing blood screening for dengue disease at different blood donation services and units in Saudi Arabia to improve the guarantee of blood transfusions and to control DENV dissemination.

Risk assessment of dengue fever in Qatar

Background: Dengue Fever constitutes a major international public health concern due to rapid expansion of geographic distribution of the virus and the mosquito vector of the disease. In this paper we aim to review the risk of Dengue Fever introduction to Qatar. Methods: Review of the Literature for the factors responsible for the worldwide spread of dengue fever and assess these factors in Qatar. Results: Internationally, the Global Climate Change is believed to be responsible of Dengue geographical expansion. High Temperature and humidity in Qatar are suitable climatic conditions for breeding of Dengue vectors Aedes aegypti and albopticus. The rapid urbanization in Qatar constitutes a favorable environment for breeding sites of Dengue vectors, as the mosquito prefers to breed in artificial containers such as discarded tires, drums, cans, buckets, flower pots, and vases. High number of international travelers, especially form dengue endemic countries to Qatar is a very important risk factor. The rapid human population growth in Qatar if combined with circulation of different dengue virus serotypes is an important risk factor for development of sever forms of Dengue Fever. Unspecific clinical presentation in addition to presence of asymptomatic dengue cases poses a challenge to the diagnosis capability of medical doctors in Qatar and hence to under reporting of dengue. Conclusion: Dengue Fever is an imminent risk to Qatar. Entomological survey is needed to determine the presence, capacity and density of Dengue Vector in Qatar. Strengthen Dengue surveillance in international travelers will work as sentinel for dengue risk in Qatar.

Tetravalent Dengue Vaccine Reduces Symptomatic and Asymptomatic Dengue Virus Infections in Healthy Children and Adolescents Aged 2-16 Years in Asia and Latin America.

Background. Asymptomatic dengue virus–infected individuals are thought to play a major role in dengue virus transmission. The efficacy of the recently approved quadrivalent CYD-TDV dengue vaccine against asymptomatic dengue virus infection has not been previously assessed.Methods. We pooled data for 3 736 individuals who received either CYD-TDV or placebo at 0, 6, and 12 months in the immunogenicity subsets of 2 phase 3 trials (clinical trials registration NCT01373281 and NCT01374516). We defined a seroconversion algorithm (ie, a ≥4-fold increase in the neutralizing antibody titer and a titer of ≥40 from month 13 to month 25) as a surrogate marker of asymptomatic infection in the vaccine and placebo groups.Results. The algorithm detected seroconversion in 94% of individuals with a diagnosis of virologically confirmed dengue between months 13 and 25, validating its discriminatory power. Among those without virologically confirmed dengue (n = 3 669), 219 of 2 485 in the vaccine group and 157 of 1 184 in the placebo group seroconverted between months 13 and 25, giving a vaccine efficacy of 33.5% (95% confidence interval [CI], 17.9%–46.1%) against asymptomatic infection. Vaccine efficacy was marginally higher in subjects aged 9–16 years (38.6%; 95% CI, 22.1%–51.5%). The annual incidence of asymptomatic dengue virus infection in this age group was 14.8%, which was 4.4 times higher than the incidence for symptomatic dengue (3.4%).Conclusions. The observed vaccine efficacy against asymptomatic dengue virus infections is expected to translate into reduced dengue virus transmission if sufficient individuals are vaccinated in dengue-endemic areas.

The risk of dengue for non-immune foreign visitors to the 2016 summer olympic games in Rio de Janeiro, Brazil.

BackgroundRio de Janeiro in Brazil will host the Summer Olympic Games in 2016. About 400,000 non-immune foreign tourists are expected to attend the games. As Brazil is the country with the highest number of dengue cases worldwide, concern about the risk of dengue for travelers is justified.MethodsA mathematical model to calculate the risk of developing dengue for foreign tourists attending the Olympic Games in Rio de Janeiro in 2016 is proposed. A system of differential equation models the spread of dengue amongst the resident population and a stochastic approximation is used to assess the risk to tourists. Historical reported dengue time series in Rio de Janeiro for the years 2000-2015 is used to find out the time dependent force of infection, which is then used to estimate the potential risks to a large tourist cohort. The worst outbreak of dengue occurred in 2012 and this and the other years in the history of Dengue in Rio are used to discuss potential risks to tourists amongst visitors to the forthcoming Rio Olympics.ResultsThe individual risk to be infected by dengue is very much dependent on the ratio asymptomatic/symptomatic considered but independently of this the worst month of August in the period studied in terms of dengue transmission, occurred in 2007.ConclusionsIf dengue returns in 2016 with the pattern observed in the worst month of August in history (2007), the expected number of symptomatic and asymptomatic dengue cases among tourists will be 23 and 206 cases, respectively. This worst case scenario would have an incidence of 5.75 (symptomatic) and 51.5 (asymptomatic) per 100,000 individuals.

DENGUE: AN OVERVIEW

ABSTRACT Dengue is one of the highest occurring vector-borne diseases. It is caused by dengue viruses 1- 4. Currently, the disease is classified into dengue with or without warning signs and severe dengue based on WHO 2009 dengue classification. As of today, neither specific drugs nor commercial vaccine exist for dengue. The best treatment yet would be support, management and proper medical care. With no pathognomonic features that could differentiate it from other febrile illnesses, clinical diagnosis alone is insufficient. Yet, despite the current advances and existence of various laboratory diagnostic methods of dengue, a consensus singular method has not been established. There are several hypotheses or theories regarding the vaguely understood immunopathogenesis of dengue. Amongst these are the viral factors, host-immune factors and host-genetic factors. In addition to these, the occurrence of asymptomatic dengue has further complicated the disease. However, these individuals provide opportunities in the search for protective factors against dengue.

Lack of Clinical Manifestations in Asymptomatic Dengue Infection Is Attributed to Broad Down-Regulation and Selective Up-Regulation of Host Defence Response Genes

ObjectivesDengue represents one of the most serious life-threatening vector-borne infectious diseases that afflicts approximately 50 million people across the globe annually. Whilst symptomatic infections are frequently reported, asymptomatic dengue remains largely unnoticed. Therefore, we sought to investigate the immune correlates conferring protection to individuals that remain clinically asymptomatic.MethodsWe determined the levels of neutralizing antibodies (nAbs) and gene expression profiles of host immune factors in individuals with asymptomatic infections, and whose cognate household members showed symptoms consistent to clinical dengue infection.ResultsWe observed broad down-regulation of host defense response (innate, adaptive and matrix metalloprotease) genes in asymptomatic individuals as against symptomatic patients, with selective up-regulation of distinct genes that have been associated with protection. Selected down-regulated genes include: TNF α (TNF), IL8, C1S, factor B (CFB), IL2, IL3, IL4, IL5, IL8, IL9, IL10 and IL13, CD80, CD28, and IL18, MMP8, MMP10, MMP12, MMP15, MMP16, and MMP24. Selected up-regulated genes include: RANTES (CCL5), MIP-1α (CCL3L1/CCL3L3), MIP-1β (CCL4L1), TGFβ (TGFB), and TIMP1.ConclusionOur findings highlight the potential association of certain host genes conferring protection against clinical dengue. These data are valuable to better explore the mysteries behind the hitherto poorly understood immunopathogenesis of subclinical dengue infection.

Asymptomatic Dengue Infection in a Cuban Population Confirms the Protective Role of the RR Variant of the FcγRIIa Polymorphism

The role of human Fcgamma receptors (FcgammaR) has been recognized considerably over the last years. These receptors vary in their affinity for IgG subclasses and the intracellular signals elicited by them. Allelic variants of FcgammaR genes may influence the biological phagocyte activity, accounting for an inherited pre-disposition to disease. The specific FcgammaRIIa (CD32) contains a polymorphic variant (H/R131) that has been associated to a reduced risk for developing dengue hemorrhagic fever (DHF). Here, we investigated the role of this polymorphism in a very well-characterized group of Cuban individuals with antecedents of DHF, dengue fever (DF), or subclinical dengue infection. The HH131 genotype was significantly associated with dengue disease, either DF (*P = 0.016; odds ratio = 4.425; 95% confidence interval = 1.10-20.52) or DHF (P = 0.00018; odds ratio = 10.56; 95% confidence interval = 2.33-54.64) with respect to the subclinical infection.

IgG Subclass and the FcG Receptor Iia Polymorphism Associate to Dengue Fever, Dengue Hemorrhagic Fever and Asymptomatic Dengue Infection in Cuba

Background: FcG Receptors II (FcGRII) mediate a variety of biological response, including Antibodies Dependent Enhancement (ADE). The ADE theory shows that the presence of circulating dengue-specific IgG antibodies can enhance the viral entry trough FcGR and constitutes the largest risk factor for the individuals to develop of Dengue Hemorrhagic Fiver (DHF). An Arginine (R) to Histidine (H) substitution at position 131 of the FcGRIIa gene change the IgG binding affinity of the receptor with reduced opsonization of IgG2 associated with the arginine variant. The exceptional epidemiological circumstances in Cuba allow us to maintain a homogeneous sample with a similar history of natural dengue virus infections. In this work we investigate whether homozygosity for the arginine variant might be associated with a reduced risk of DHF caused by ADE and the subclass of IgG in the acute serum samples from individuals who suffered secondary infection to dengue 2 virus in the epidemic of Santiago de Cuba in 1997 with different clinical pictures. Methods: The Subclass of IgG were detected using Dot Blot in the soluble fraction and the immunocomplex fraction of the dengue acute serum samples kinetically collected. The DNA samples were studied to determine the polymorphism associated to Fc gamma receptor IIa. The FcGRIIa genotypes (R/R131, H/H131 and R/H131) and allelic frequencies were compared. Results: IgG1 are the predominant IgG subclass during the dengue acute infection even as a part of the immunocomplex or free in the serum. On the other hand IgG3 levels, only detected in the immunocomplex fraction, were observed in DF cases. The distribution of FcGRIIa genotype frequencies in Santiago de Cuba population showed the predominant RH genotype and the homozygocity for arginine variant did not found any protective effect associate to dengue infection in our population. Conclusion: The IgG subclass involved in dengue infection are IgG1 and IgG3 and the ADE phenomenon probably take place by the FcGRIIIa and FcGRIIIb associate with these IgG.