Clinical and Virological Study of Dengue Cases and the Members of Their Households: The Multinational DENFRAME Project

Dengue is the most important mosquito-borne viral disease in humans. This disease is now endemic in more than 100 countries and threatens more than 2.5 billion people living in tropical countries. It currently affects about 50 to 100 million people each year. It causes a wide range of symptoms, from an inapparent to mild dengue fever, to severe forms, including dengue hemorrhagic fever. Currently no specific vaccine or antiviral drugs are available. We carried out a prospective clinical study in South-East Asia and Latin America, of virologically confirmed dengue-infected patients attending the hospital, and members of their households. Among 215 febrile dengue subjects, 177 agreed to household investigation. Based on our data, we estimated the proportion of dengue-infected household members to be about 45%. At the time of the home visit, almost three quarters of (29/39) presented an inapparent dengue infection. The proportion of inapparent dengue infection was higher in South-East Asia than in Latin America. These findings confirm the complexity of dengue disease in humans and the need to strengthen multidisciplinary research efforts to improve our understanding of virus transmission and host responses to dengue virus in various human populations

Main characteristics of subjects with inapparent dengue infections compared to non-dengue-infected subjects among Household members.

<p>*Potential confounders with a P value of less than 0.20 in univariate analysis were retained for the final multivariable analyses. In this table: age, platelets, neutrophils, lymphocytes, ASAT and IgG at Visit 1.</p>a<p>ASAT: Aspartate amino transferase.</p>b<p>ALAT: Alanine amino transferase.</p><p>Univariate and multivariable logistic regression were used for analyses.</p

Characteristics of dengue index cases (DIC, n = 215).

<p>*For 3 subjects infected by DENV-2, data related to IgG status were missing: 2 dengue fever cases and 1 severe dengue case.</p><p>Distribution of DIC is provided by region in relation to the presence of WHO criteria for severe dengue and IgG status during the acute phase.</p

Localization of the four clinical sites.

<p>A: in South-East Asia (Cambodia and Vietnam). B in Latin America (Brazil and French Guiana).</p

Main characteristics of subjects with inapparent dengue infections compared to symptomatic dengue-infected subjects.

<p>*Potential confounders with a P value of less than 0.20 in univariate analysis were retained for the final multivariable analyses. In this table: weight-based Z-score, platelets, neutrophils, lymphocytes, monocytes, ASAT, ALAT and NS1 antigen.</p>a<p>ASAT: Aspartate amino transferase.</p>b<p>ALAT: Alanine amino transferase.</p><p>Univariate and multivariable logistic regression were used for analyses.</p

Study design for the inclusion of patients.

<p>A: Step 1, identification of dengue index cases (DIC) and non-dengue-infected cases (NDC). B: Step 2, Identification of household members (HHM).</p

Distribution of the participants in the clinical study (n = 590).

<p>All participants were identified at Visit 1 for Dengue Index Cases (DIC) and at Home Visit 1 for dengue-infected household members (HHM). Their distribution is presented by country, according to DENV-infected status and IgG status.</p