[show abstract][hide abstract] ABSTRACT: Recognizing the uniqueness of secondary dengue virus (DENV)-1/3 dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS) cases at an interval of 24 years, we sought to estimate DENV infections as well as the ratios between mild disease and DHF/DSS by DENV infection sequence in Playa District (Havana, Cuba) during the 2001-2002 outbreak of dengue virus type 3 (DENV-3).
A retrospective seroepidemiological study was conducted in 2003 in Playa District. Blood samples were collected from a 1% random sample of residents and were studied for the prevalence of dengue neutralizing antibodies.
DENV-3 was found to have infected 7.2% (95% confidence interval (95% CI) 6.0-8.4%) of susceptible individuals (the entire cohort), the majority of whom experienced silent infections. Virtually every individual who had a secondary infection in the sequence DENV-1 then DENV-3 became ill, with a ratio of severe to mild cases of 1:35 (95% CI 1:67-1:23). Secondary infections in the sequence DENV-2/3 were less pathogenic than DENV-1/3. Mild disease accompanying secondary DENV2/3 occurred at a ratio of 1:4.49 infections (95% CI 1:5.77-1:3.42) secondary infections.
The results obtained highlight the role of the infecting serotype and also the sequence of the viral infection in the clinical outcome of a dengue infection.
International journal of infectious diseases: IJID: official publication of the International Society for Infectious Diseases 03/2012; 16(3):e198-203. · 2.17 Impact Factor
[show abstract][hide abstract] ABSTRACT: Determine point prevalence of febrile syndromes and compare with prevalence reported by habitual clinical and seroepidemiologic dengue surveillance system in Havana City.
In October 2007, a descriptive, cross-sectional study was carried out in a representative sample, calculating prevalences of febrile syndromes and undifferentiated febrile syndromes. Chi-square analysis was used for rate comparisons.
Point prevalences of febrile syndromes and undifferentiated febrile syndromes were 352.6 and 144.2 times greater, respectively, than those reported by the habitual clinical and seroepidemiologic dengue surveillance system; these differences were statistically significant (p < 0.001).
Point prevalence of febrile syndromes was far greater than prevalence reported by the habitual clinical and seroepidemiologic dengue surveillance system, an indication of underreporting.
[show abstract][hide abstract] ABSTRACT: Dengue epidemics in Cuba have repeatedly demonstrated a month-to-month increase in clinical severity during secondary infections. The dengue 2 outbreak that occurred in Santiago de Cuba in 1997 was accompanied by the most severe intraepidemic increase in disease severity reported to date. It was initially proposed that the appearance of neutralization escape mutants during the course of the epidemic might explain this phenomenon. Recent studies have revealed that during the course of this epidemic, nucleotide substitutions appeared only in nonstructural (NS) genes, most of which were silent, except for one change in the NS1 gene. To study whether or not variation in the NS1 gene might be associated with increased disease severity during the epidemic, this gene was partially sequenced from 15 isolates obtained at different times during the 1997 epidemic. Early epidemic isolates differed from those obtained later by replacement only of threonine with serine at position 164 in the NS1 protein, an amino acid rarely found in any genotype of dengue 2 virus. All viruses isolated from patients located in Health Districts, where dengue 2 transmissions occurred late in the epidemic, contained Serine at position 164, indicating that this change was fixed within a few months. Here we argue that this single mutation contributes to viral survival or replication efficiency, resulting in enhanced infection in the presence of enhancing antibodies, a phenomenon that we term increased virus "fitness" in contrast to "virulence," an intrinsic property of the virus.
[show abstract][hide abstract] ABSTRACT: Increased serum levels of cytokines released by cells of the immune response have been detected in patients suffering from dengue disease. Likewise, secondary infections by a different dengue virus serotype result in a highest risk of development of the severe dengue disease. Both findings suggest that the memory immune response is one of the key players in the pathogenesis of this disease. Here we take advantage of the particular Cuban epidemiological situation in dengue to analyze a broad spectrum of cell-mediated immune response mediators at mRNA and protein level. Evidences for a regulatory immune pattern in homologous (TGF-beta, IL-10) vs. pro-inflammatory pattern (IFN-gamma, TNF-alpha) in heterologous dengue virus re-challenge were found, suggesting a possible association with the higher incidence of severe dengue cases in the latter case.
[show abstract][hide abstract] ABSTRACT: To document the process, outcome and effectiveness of a community-based intervention for dengue control.
The primary intervention, focused on strengthening intersectoral coordination, was initiated by researchers in January 2000 in a pilot area in Playa municipality, Havana. In August 2002 health authorities extended the intervention to neighbouring areas, one of which was selected for evaluation. In August 2003 a complementary strategy, focused on community empowerment, was initiated in half of the pilot area. In our control area, routine dengue activities continued throughout the study period. Longitudinal process assessment was carried out using document analysis, interviews and group discussions. Random population surveys in 1999, 2002 and 2005 assessed levels of participation and behavioural changes. Entomological surveillance data from 1999 to 2005 were used to determine effectiveness.
Mean scores for participation in the pilot area were 1.6, 3.4 and 4.4 at baseline, and 2 years after initiating intersectoral coordination and intersectoral coordination plus community empowerment interventions, respectively. While in the control area little behavioural change was observed over time, changes were considerable in the pilot and extension areas, with 80% of households involved in the community empowerment intervention showed adequate behavioural patterns. The pilot and extension areas attained comparable entomological effectiveness with significantly lower Breteau indices (BIs) than the control area. The pilot (sub-) area with the community empowerment intervention reached BIs below 0.1 that continued to be significantly lower than the one in the control area until the end of the study.
The study showed a trend in the levels and quality of participation, behavioural change and effectiveness of Aedes control from the routine activities only over an intervention with intersectoral coordination to one that combined intersectoral coordination and community empowerment approach.
Tropical Medicine & International Health 11/2009; 14(11):1356-64. · 2.94 Impact Factor
[show abstract][hide abstract] ABSTRACT: Over a decade ago, the Commission on Health Research for Development published a pioneering study on the gross imbalance between the world's research funding priorities and global disease burden distribution. This study reported that less than 10% of world resources for health research were being applied to the health problems of developing countries, where 90% of the avoidable burden of ill-health was to be found. What became known as the "10/90 gap" has captured the attention and imagination of those committed to global health equity everywhere, searching for ways to incline the research agenda towards "diseases of the poor".
[show abstract][hide abstract] ABSTRACT: A randomized, double-blind, placebo-controlled clinical trial was conducted to evaluate the safety, reactogenicity and the immunogenicity of a 2 x 10(9)CFU dose of the 638 lyophilized live attenuated cholera vaccine for oral administration, formulated and produced at Finlay Institute, City of Havana, Cuba. Thirty-six healthy female and male adult volunteers from 18 to 40 years old were involved, clinically examined and laboratory tested after the informed consent signature. Adverse events were monitored and seroconversion rates and geometrical mean titer (GMT) of vibriocidal antibodies were tested in volunteer's sera samples. Neither serious adverse events nor other damages to the volunteers due to vaccine or placebo feeding were reported during the clinical follow-up period of this study; none of the adverse events registered within the first 72 h after inoculation were life-threatening for volunteers. Neither severe nor moderate adverse events were reported. Sixty-one percent of subjects showed mild expected adverse events in an interval lower than 24h up to the first 72 h, 75% of these in the vaccinated group and 18% in the placebo group. Fourteen days after inoculation the GMT of vibriocidal antibodies in the vaccine group significantly increased in comparison to the placebo group. All subjects in the vaccine group (24) seroconverted (100%). Results show that this vaccine is safe, well tolerated and immunogenic in healthy female and male volunteers.
[show abstract][hide abstract] ABSTRACT: Dengue is considered the main arthropod-borne viral disease of humans. In the last few years, an increasing number of reports of mild and severe cases have been reported. The growing dengue incidence observed in recent years has been accompanied by reports of new observations, findings and global initiatives with an improvement in our understanding of this phenomenon. The epidemiology and new clinical classification of dengue, advances in the diagnostic and pathogenesis knowledge, and vaccine development as well as control methods including new global initiatives are summarised here.
Malaysian Journal of Medical Sciences 07/2009; 16(3):4-11.
[show abstract][hide abstract] ABSTRACT: Although dengue virus (DEN) endemic regions overlap with human immunodeficiency virus 1 (HIV) high incidence areas, little has been documented on HIV and DEN mixed infection. Here we report DEN/HIV concurrent infections recorded during the DEN-3 epidemic in 2001-2002 in Havana. Serologic-confirmed DEN is described in two HIV-infected subjects with dengue fever symptoms. Although patients had dengue disease, the CD4+ cells remained within normal levels and no accelerated progression of HIV disease was observed. To our knowledge, DEN cases caused by DEN-3 in HIV-infected individuals have not been reported previously. Further research is needed to diagnose this likely underreported mixed viral infection in DEN endemic areas.
The Journal of Infection in Developing Countries 01/2009; 3(4):318-20. · 1.00 Impact Factor
[show abstract][hide abstract] ABSTRACT: To document the process and analyze the results of implementing a strategy aimed at increasing community participation in the fight against the dengue mosquito vector.
From May 2002 to May 2004, an intervention was implemented to advance social action against dengue in three districts of the municipality of Playa, La Habana, Cuba. A learning group and community working groups (CWG) were organized in each location. A community education model was followed that combines putting the plan of action into practice, with sessions to reflect and learn from the results, and then reworking of the actions for subsequent stages. Diagnostic tools were developed for communities, preventative actions, communication, surveillance, and evaluation. Changes in participation were identified by applying the content analysis technique to the documents and through interviews with key informants.
The community work advanced at a pace relative to the abilities and interests of each community with different areas of focus: healthy community, environmental risk, and entomological risk. Positive changes in the concept of participation were obtained, according to the five areas evaluated: leadership, needs assessment, organization, management, and mobilization of resources. At the end of two years of intervention, the rate of Aedes aegypti larvae and pupae deposits found per 100 households had declined 79% and cases of dengue were not detected in any of the districts.
This strategy reduced mosquito vector infestation levels by increasing community participation in decision-making and strengthening the competencies of the medical teams and CWGs so that they lead participative processes in the community and raised confidence in their ability to achieve change with the appropriate resources and intersectoral support.
Revista Panamericana de Salud Pública 08/2008; 24(1):61-9. · 0.85 Impact Factor
[show abstract][hide abstract] ABSTRACT: In 1987, Kouri et al. published in Transactions their integral hypothesis to explain the development of dengue haemorrhagic fever (DHF) epidemics (Kouri, G.P., Guzmán, M.G., Bravo, J.R., 1987. Why dengue haemorrhagic fever in Cuba? 2. An integral analysis. Trans. R. Soc. Trop. Med. Hyg. 81, 821-823). Based on observations carried out during the 1981 Cuban DHF epidemic, the authors integrated in one model the most advanced knowledge at that time. Observations in the last 20 years confirm the importance of this multifactorial and unifying view of the problem, where the interaction between the host, the virus and the vector in an epidemiological and ecosystem setting might determine DHF as a final outcome. Investigations on the interaction among host, virus and mosquito with an ecosystemic view are needed.
Transactions of the Royal Society of Tropical Medicine and Hygiene 07/2008; 102(6):522-3. · 1.82 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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.
Instrumental case study based on an exhaustive content analysis of project documents and on observations of a sociologist.
The context and the pilot project are systematically described and an analysis of the evolution of the underlying concept of community participation is provided. The pilot experience was a dynamic process influenced by self-reflection of the research team, feedback from research partners and changes in the epidemiological context (provoked by two dengue outbreaks during the study period). Community participation evolved from being just one component in Aedes aegypti control directed by the health staff into a learning and empowering process for the people. This change in the concept of participation was reflected in different aspects of the pilot project such as the learning and evaluation processes.
Empirical evidence from 5 years of research in the particular context of Cuba showed that moves towards community-based Aedes aegypti control are feasible. However, in order to be successful, community-based dengue prevention should be a social learning process, implying a transfer of power and responsibilities to local people. Actions undertaken must be oriented towards creating local capabilities, strengthening existing structures and organizations and promoting group work for learning participation from participation itself.
Tropical Medicine & International Health 06/2007; 12(5):664-72. · 2.94 Impact Factor
[show abstract][hide abstract] ABSTRACT: Severity of disease is markedly increased when infection with dengue virus type 2 (DENV-2) follows infection with DENV-1 at an interval of 20 years. Studies have shown that heterologous neutralizing antibody titers are inversely correlated with severity of a second infection. If this mechanism controlled disease severity in Cuba, heterotypic antibody titers should have declined over time. To determine whether phenotypic changes in dengue antibodies occur over time, we analyzed serum samples collected 4-8 and 20-22 years after DENV-1 infection. We found a significant increase in mean titer of homologous DENV-1 neutralizing antibodies and a significant decrease in heterologous antibodies to 1 of 2 genotypes of DENV-2 virus (the American genotype). Asian DENV-2 viruses were not neutralized during either interval; however, the American genotype underwent phenotypic changes in heterotypic viral neutralizing antibodies in the predicted direction. This finding may be related to the time-dependent changes in severity of disease found with secondary dengue infection.
[show abstract][hide abstract] ABSTRACT: Cuban DHF/DSS outbreaks have provided evidence of a reduced risk of people of Negroid race for DHF/DSS compared to those of Caucasoid race. These observations from Cuban dengue outbreaks have significant epidemiological interest, as the differences in susceptibility to DHF/DSS among racial groups in Cuba coincide with that reported in African and Black Caribbean populations. In this article, we review the literature on race as a risk factor for DHF/DSS and discuss recent results from ongoing studies. Taking into consideration the origins of contemporary Cuban inhabitants, we propose that the Cuban, Caribbean Black and African populations share a common gene pool that could explain, at least partially, the low incidence of dengue hemorrhagic fever in Cuba and Caribbean and African countries. The central role played by immunological mechanisms in the pathogenesis of DHF/DSS has led us to consider that the polymorphic genes associated with the immune response must be carefully considered among those human genes regulating dengue disease severity that might be distributed unequally in Blacks and Whites.
Archives of Virology 02/2007; 152(3):533-42. · 2.03 Impact Factor