Lizet Sánchez

Aedes aegypti larval indices and risk for dengue epidemics.

Entomologic indices can identify areas at high risk for disease transmission.

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.

Intersectoral coordination in Aedes aegypti control. A pilot project in Havana City, Cuba

Background  The 55th World Health Assembly declared dengue prevention and control a priority and urged Member States to develop sustainable intersectoral strategies to this end. To provide evidence for the reorientation of the dengue prevention policy in Cuba, we launched an intervention study to document the effectiveness of a local‐level intersectoral approach.

Long-term persistence of clinical symptoms in dengue-infected persons and its association with immunological disorders

OBJECTIVES The acute manifestations of dengue are well known. The clinical symptoms that present during the convalescent phase of infection are less well characterized, but may be autoimmune-based. This study was undertaken to determine the prevalence of persistent clinical symptoms among individuals infected during the 2006 Cuban epidemic and to evaluate the immunological and genetic factors associated with their occurrence. METHODS In 2008, clinical data and blood samples were collected from a random sample of adult individuals diagnosed during the 2006 epidemic with dengue fever (DF, n=68), dengue hemorrhagic fever (DHF, n=29), or an asymptomatic infection (AI, n=42). The presence of persistent symptoms was evaluated in all individuals and a psychological assessment was performed. IgG titers and the Fc receptor (FcR) were also evaluated. The following autoimmune markers were assessed in a subset (n=26) of symptomatic individuals: complement factors C3/C4, rheumatoid factor (RF), C-reactive protein (CRP), antinuclear antibodies (ANA), and immune complex (IC). RESULTS Over half (55/97) the individuals with a prior of diagnosis of DF or DHF had persistent clinical symptoms in the 2 years following infection. The sequelae were unrelated to the initial diagnosis and were more common among women (44/55). No symptoms were reported in the AI group and all study participants had normal mental and cognitive function. Persistent clinical symptoms were associated with HH polymorphic variant (p=0.027) and high IgG titer (p=0.041). Autoimmune marker alterations were common (20/26) in the subset of symptomatic individuals evaluated. CONCLUSIONS Clinical sequelae after recovery from an acute dengue virus infection are common in the 2 years following infection. The results obtained in this study suggest that persistent symptoms are associated with alterations in some immunological parameters and FcγRIIa gene polymorphism. This could suggest an autoimmune-based disturbance.

Dengue, one of the great emerging health challenges of the 21st century

Dengue, one of the great emerging health challenges of the 21st Century 31 May-3 June 2004, 2nd International Congress on Dengue and Yellow Fever, Havana, Cuba Maria G Guzman, Gustavo Kouri, Manuel Diaz, Alina Llop, Susana Vazquez, Daniel Gonzalez, Osvaldo Castro, Angel Alvarez, Omar Fuentes, Domingo Montada, Harish Padmanabha, Beatriz Sierra, Ana B Perez, Delfina Rosario, Maritza Pupo, Cristina Diaz and Lisette Sanchez

Community participation in Aedes aegypti control: a sociological perspective on five years of research in the health area '26 de Julio', Havana, Cuba

Objective:  Effective dengue prevention and Aedes aegypti control is a priority for the Cuban health authorities. To enhance effectiveness, strategies oriented towards a more active involvement of communities in control activities are being tested. This paper presents a sociological perspective on a pilot project conducted in the health area ‘‘26 de Julio’’ (La Havana) in 1999–2004.

Breteau Index threshold levels indicating risk for dengue transmission in areas with low Aedes infestation.

We used Breteau Indices to – retrospectively – predict dengue transmission. The presence of one house block (on average about 50 houses) with a Breteau Index ≥4 in a neighbourhood (a block plus the surrounding blocks in a radius of 100 m) predicted transmission at the latter level with 81.8% sensitivity and 73.3% specificity during the first month of the Havana 2001 dengue outbreak. This result corroborates the external validity of this threshold, at least in situations with low infestations levels.

Intersectoral coordination, community empowerment and dengue prevention: six years of controlled interventions in Playa Municipality, Havana, Cuba

Objective  To document the process, outcome and effectiveness of a community‐based intervention for dengue control.

A community empowerment strategy embedded in a routine dengue vector control programme: a cluster randomised controlled trial

The non-sustainability of vertically organised dengue vector control programmes led to pleas for changing the emphasis towards community-based strategies. We conducted a cluster randomised controlled trial with 16 intervention and 16 control clusters to test the effectiveness of a community empowerment strategy intertwined with the routine dengue vector control programme in La Lisa, Havana City, Cuba. The intervention included four components on top of routine control: organisation and management; entomological risk surveillance; capacity building; and community work for vector control. In the control clusters, routine activities continued without interference. The community participation score increased from 1.4 to 3.4. Good knowledge of breeding sites increased by 52.8% and 27.5% in the intervention and control clusters, respectively. There were no changes in adequate Aedes aegypti control practices at household level in the control clusters, but in the intervention clusters adequacy increased by 36.2%. At baseline, the Breteau indices (BI) were approximately 0.1 and were comparable; they fluctuated over time but became different with the launch of the community-based dengue control activities in the intervention clusters. Over the intervention period, the BI remained 53% (95% CI 22-92%) lower in these clusters than in the control clusters. The empowerment strategy increased community involvement and added effectiveness to routine A. aegypti control.

Association of MICA and MICB alleles with symptomatic dengue infection

Dengue viruses (DV) are one of the most important arthropod-borne viral diseases in the developing world. DV can cause syndromes that are either self-limiting or severe. Allelic variants of human leukocyte antigen (HLA) genes have been demonstrated to be associated with disease susceptibility. Here we report the association of nonclassical HLA class I MICA-MICB genes with disease outcome during DV infection. A sequencing-based typing method and genotyping of MICA and MICB in a well-characterized group of Cuban individuals with dengue hemorrhagic fever (DHF), dengue fever (DF), or asymptomatic dengue infection (ADI) was performed. Statistical analysis revealed a tendency for MICA*008 and MICB*008 to associate with susceptibility to illness when symptomatic versus asymptomatic cases (odds ratio [OR] = 2.1, p(v) = 0.03, and OR = 10.4, p = 0.0096, respectively) were compared. Surprisingly, a stronger association of both allelic forms was observed for the DF patients compared with the ADI group (MICA*008, OR = 5.2, p = 0.0001; and MICB*008, OR = 13.2, p = 0.0025) rather than the severe cases. Major histocompatibility class I-related gene-related natural killer cells and/or γδ and αβ T-cell activation might regulate the development of symptomatic DF and DHF.