María Eugenia Toledo

Community involvement in dengue vector control: cluster randomised trial

Objective To assess the effectiveness of an integrated community based environmental management strategy to control Aedes aegypti, the vector of dengue, compared with a routine strategy. Design Cluster randomised trial. Setting Guantanamo, Cuba. Participants 32 circumscriptions (around 2000 inhabitants each). Interventions The circumscriptions were randomly allocated to control clusters (n=16) comprising routine Aedes control programme (entomological surveillance, source reduction, selective adulticiding, and health education) and to intervention clusters (n=16) comprising the routine Aedes control programme combined with a community based environmental management approach. Main outcome measures The primary outcome was levels of Aedes infestation: house index (number of houses positive for at least one container with immature stages of Ae aegypti per 100 inspected houses), Breteau index (number of containers positive for immature stages of Ae aegypti per 100 inspected houses), and the pupae per inhabitant statistic (number of Ae aegypti pupae per inhabitant). Results All clusters were subjected to the intended intervention; all completed the study protocol up to February 2006 and all were included in the analysis. At baseline the Aedes infestation levels were comparable between intervention and control clusters: house index 0.25% v 0.20%, pupae per inhabitant 0.44×10−3 v 0.29×10−3. At the end of the intervention these indices were significantly lower in the intervention clusters: rate ratio for house indices 0.49 (95% confidence interval 0.27 to 0.88) and rate ratio for pupae per inhabitant 0.27 (0.09 to 0.76). Conclusion A community based environmental management embedded in a routine control programme was effective at reducing levels of Aedes infestation. Trial registration Current Controlled Trials ISRCTN88405796.Objective To assess the effectiveness of an integrated community based environmental management strategy to control Aedes aegypti, the vector of dengue, compared with a routine strategy. Design Cluster randomised trial. Setting Guantanamo, Cuba. Participants 32 circumscriptions (around 2000 inhabitants each). Interventions The circumscriptions were randomly allocated to control clusters (n=16) comprising routine Aedes control programme (entomological surveillance, source reduction, selective adulticiding, and health education) and to intervention clusters (n=16) comprising the routine Aedes control programme combined with a community based environmental management approach. Main outcome measures The primary outcome was levels of Aedes infestation: house index (number of houses positive for at least one container with immature stages of Ae aegypti per 100 inspected houses), Breteau index (number of containers positive for immature stages of Ae aegypti per 100 inspected houses), and the pupae per inhabitant statistic (number of Ae aegypti pupae per inhabitant). Results All clusters were subjected to the intended intervention; all completed the study protocol up to February 2006 and all were included in the analysis. At baseline the Aedes infestation levels were comparable between intervention and control clusters: house index 0.25% v 0.20%, pupae per inhabitant 0.44×10−3 v 0.29×10−3. At the end of the intervention these indices were significantly lower in the intervention clusters: rate ratio for house indices 0.49 (95% confidence interval 0.27 to 0.88) and rate ratio for pupae per inhabitant 0.27 (0.09 to 0.76). Conclusion A community based environmental management embedded in a routine control programme was effective at reducing levels of Aedes infestation. Trial registration Current Controlled Trials ISRCTN88405796.

Antigenicity and Immunogenicity of a Synthetic Oligosaccharide-Protein Conjugate Vaccine against Haemophilus influenzae Type b

ABSTRACT Polysaccharide-protein conjugates as vaccines have proven to be very effective in preventing Haemophilus influenzae type b infections in industrialized countries. However, cost-effective technologies need to be developed for increasing the availability of anti-H. influenzae type b vaccines in countries from the developing world. Consequently, vaccine production with partially synthetic antigens is a desirable goal for many reasons. They may be rigidly controlled for purity and effectiveness while at the same time being cheap enough that they may be made universally available. We describe here the antigenicity and immunogenicity of several H. influenzae type b synthetic oligosaccharide-protein conjugates in laboratory animals. The serum of H. influenzae type b-immunized animals recognized our synthetic H. influenzae type b antigens to the same extent as the native bacterial capsular polysaccharide. Compared to the anti-H. influenzae type b vaccine employed, these synthetic versions induced similar antibody response patterns in terms of titer, specificity, and functional capacity. The further development of synthetic vaccines will meet urgent needs in the less prosperous parts of the world and remains our major goal.

Phase I Clinical Evaluation of a Synthetic Oligosaccharide-Protein Conjugate Vaccine against Haemophilus influenzae Type b in Human Adult Volunteers

ABSTRACT Since 1989, we have been involved in the development of a vaccine against Haemophilus influenzae type b. The new vaccine is based on the conjugation of synthetic oligosaccharides to tetanus toxoid. Our main goals have been (i) to verify the feasibility of using the synthetic antigen and (ii) to search for new production alternatives for this important infant vaccine. Overall, eight trials have already been conducted with adults, children (4 to 5 years old), and infants. We have described herein the details from the first two phase I clinical trials conducted with human adult volunteers under double blind, randomized conditions. The participants each received a single intramuscular injection to evaluate safety and initial immunogenicity. We have found an excellent safety profile and an antibody response similar to the one observed for the control vaccine.

Process-oriented fidelity research assists in evaluation, adjustment and scaling-up of community-based interventions

Fidelity research can help to answer essential questions about the diffusion process of innovative health interventions and provide insights for further scaling-up and institutionalization. This study assessed fidelity and reinvention in the implementation of a community-based control strategy for Aedes aegypti control. The intervention was implemented in 16 study areas in La Lisa, a municipality of Havana, Cuba. Its major components were: organization & management, capacity-building, community work and surveillance. A participatory assessment of process data was performed to determine whether the components and subcomponents were implemented, not-implemented or modified. Frequencies were tabulated over all circumscriptions (lowest level of local government) and the average was calculated for the four components. Spearman Rank correlation coefficients were calculated to explore the relationships between components. In addition, semi-structured interviews were conducted with co-ordinators of the strategy at different levels to identify difficulties encountered in the strategys implementation. Surveillance was the most implemented component (72.9%) followed by capacity-building (54.7%). Community work and organization & management were less implemented or modified (50% and 45%, respectively). Apart from surveillance and capacity-building, all components are significantly and strongly correlated (Spearman Rank correlation coefficient > 0.70, P < 0.01). If one component is implemented in a circumscription, the other components are also likely to be implemented. It is noticeable that areas which did not undergo organizational changes commonly did not implement community work activities. Within the whole strategy, few activities were added. Scarcely implemented subcomponents were the most innovative. The difficulties encountered during implementation were related to appropriate training and skills, available time, lack of support and commitment to the strategy, lack of motivation of local leadership, and integration of actors and resources. The study showed a wide variability of fidelity in the implementation of the intervention and highlighted challenges for scaling-up and institutionalization of the community-based intervention.

The unbearable lightness of technocratic efforts at dengue control

Objective  To identify key elements that should provide an added value and assure sustainable effects of the deployment of technical tools for Aedes aegypti control.

Costs of dengue prevention and incremental cost of dengue outbreak control in Guantanamo, Cuba.

Objective  To assess the economic cost of routine Aedes aegypti control in an at‐risk environment without dengue endemicity and the incremental costs incurred during a sporadic outbreak.

Evidence on impact of community-based environmental management on dengue transmission in Santiago de Cuba

During the dengue outbreak that struck Santiago de Cuba in 2006–2007, we conducted an observational study in the Mariana Grajales district, the former setting of a community trial for Aedes aegypti control. In the trial, community working groups (CWG) had been created in 29 randomly selected intervention house blocks, and routine vector control activities alone were conducted in the remaining 30 control blocks. The CWG elaborated and implemented with the population plans and activities to reduce Aedes infestation. They were still functional in 2006 and continued organizing community‐based environmental management activities. The attack rate of dengue fever during the outbreak was 8.5 per 1000 inhabitants in the former intervention blocks and 38.1 per 1000 inhabitants in the control blocks, which corresponds to a relative risk of 4.5 (95% CI 3.1–6.5). There was a significantly higher proportion of unaffected intervention blocks, and affected blocks had on average substantially less cases than affected control blocks. This study indicates that community‐based environmental management inserted in the routine A. aegypti control programme can not only sustainably curb vector infestation but also have an impact on dengue transmission.

No Effect of Insecticide Treated Curtain Deployment on Aedes Infestation in a Cluster Randomized Trial in a Setting of Low Dengue Transmission in Guantanamo, Cuba

Objective & Methodology The current study evaluated the effectiveness and cost-effectiveness of Insecticide Treated Curtain (ITC) deployment for reducing dengue vector infestation levels in the Cuban context with intensive routine control activities. A cluster randomized controlled trial took place in Guantanamo city, east Cuba. Twelve neighborhoods (about 500 households each) were selected among the ones with the highest Aedes infestation levels in the previous two years, and were randomly allocated to the intervention and control arms. Long lasting ITC (PermaNet) were distributed in the intervention clusters in March 2009. Routine control activities were continued in the whole study area. In both study arms, we monitored monthly pre- and post-intervention House Index (HI, number of houses with at least 1 container with Aedes immature stages/100 houses inspected), during 12 and 18 months respectively. We evaluated the effect of ITC deployment on HI by fitting a generalized linear regression model with a negative binomial link function to these data. Principal Findings At distribution, the ITC coverage (% of households using ≥1 ITC) reached 98.4%, with a median of 3 ITC distributed/household. After 18 months, the coverage remained 97.4%. The local Aedes species was susceptible to deltamethrin (mosquito mortality rate of 99.7%) and the residual deltamethrin activity in the ITC was within acceptable levels (mosquito mortality rate of 73.1%) after one year of curtain use. Over the 18 month observation period after ITC distribution, the adjusted HI rate ratio, intervention versus control clusters, was 1.15 (95% CI 0.57 to 2.34). The annualized cost per household of ITC implementation was 3.8 USD, against 16.8 USD for all routine ACP activities. Conclusion Deployment of ITC in a setting with already intensive routine Aedes control actions does not lead to reductions in Aedes infestation levels.

Incremental cost of implementing residual insecticide treatment with delthametrine on top of intensive routine Aedes aegypti control

Information on the cost of implementing residual insecticide treatment (RIT) for Aedes control is scarce. We evaluated the incremental cost on top of intensive conventional routine activities of the Aedes control programme (ACP) in the city of Santiago de Cuba, Cuba.

Cost of intensive routine control and incremental cost of insecticide-treated curtain deployment in a setting with low Aedes aegypti infestation.

INTRODUCTION Information regarding the cost of implementing insecticide-treated curtains (ITCs) is scarce. Therefore, we evaluated the ITC implementation cost, in addition to the costs of intensive conventional routine activities of the Aedes control program in the city of Guantanamo, Cuba. METHODS A cost-analysis study was conducted from the perspective of the Aedes control program, nested in an ITC effectiveness trial, during 2009-2010. Data for this study were obtained from bookkeeping records and activity registers of the Provincial Aedes Control Programme Unit and the account records of the ITC trial. RESULTS The annual cost of the routine Aedes control program activities was US