Identifying individual predictive factors for treatment efficacy.

Given the heterogeneous responses to therapy and the high cost of treatments, there is an increasing interest in identifying pretreatment predictors of therapeutic effect. Clearly, the success of such an endeavor will depend on the amount of information that the patient-specific variables convey about the individual causal treatment effect on the response of interest. In the present work, using causal inference and information theory, a strategy is proposed to evaluate individual predictive factors for cancer immunotherapy efficacy. In a first step, the methodology proposes a causal inference model to describe the joint distribution of the pretreatment predictors and the individual causal treatment effect. Further, in a second step, the so-called predictive causal information (PCI), a metric that quantifies the amount of information the pretreatment predictors convey on the individual causal treatment effects, is introduced and its properties are studied. The methodology is applied to identify predictors of therapeutic success for a therapeutic vaccine in advanced lung cancer. A user-friendly R library EffectTreat is provided to carry out the necessary calculations.

Identifying predictive biomarkers of CIMAvaxEGF success in non-small cell lung cancer patients.

BACKGROUND: Immunosenescence biomarkers and peripheral blood parameters are evaluated separately as possible predictive markers of immunotherapy. Here, we illustrate the use of a causal inference model to identify predictive biomarkers of CIMAvaxEGF success in the treatment of Non-Small Cell Lung Cancer Patients. METHODS: Data from a controlled clinical trial evaluating the effect of CIMAvax-EGF were analyzed retrospectively, following a causal inference approach. Pre-treatment potential predictive biomarkers included basal serum EGF concentration, peripheral blood parameters and immunosenescence biomarkers. The proportion of CD8 + CD28- T cells, CD4+ and CD8+ T cells, CD4/CD8 ratio and CD19+ B cells. The 33 patients with complete information were included. The predictive causal information (PCI) was calculated for all possible models. The model with a minimum number of predictors, but with high prediction accuracy (PCI > 0.7) was selected. Good, rare and poor responder patients were identified using the predictive probability of treatment success. RESULTS: The mean of PCI increased from 0.486, when only one predictor is considered, to 0.98 using the multivariate approach with all predictors. The model considering the proportion of CD4+ T cell, basal Epidermal Growth Factor (EGF) concentration, neutrophil to lymphocyte ratio, Monocytes, and Neutrophils as predictors were selected (PCI > 0.74). Patients predicted as good responders according to the pre-treatment biomarkers values treated with CIMAvax-EGF had a significant higher observed survival compared with the control group (p = 0.03). No difference was observed for bad responders. CONCLUSIONS: Peripheral blood parameters and immunosenescence biomarkers together with basal EGF concentration in serum resulted in good predictors of the CIMAvax-EGF success in advanced NSCLC. Future research should explore molecular and genetic profile as biomarkers for CIMAvax-EGF and it combination with immune-checkpoint inhibitors. The study illustrates the application of a new methodology, based on causal inference, to evaluate multivariate pre-treatment predictors. The multivariate approach allows realistic predictions of the clinical benefit of patients and should be introduced in daily clinical practice.

[Translation into practice of empowerment strategies for dengue prevention: facilitators and barriers]. / Traslación a la práctica de estrategias de empoderamiento en la prevención del dengue: facilitadores y barreras.

Objective To identify facilitators and barriers to the process of translating community empowerment strategies into the practice of the national Aedes aegypti control program in Cuba. Methods A case study of the process was conducted from 2005 to 2009 at national and provincial levels of the control program. Data from participant observation, in-depth interviews, and document analysis were triangulated and analyzed inductively and deductively. Results The main facilitators identified included a proposal for an empowerment strategy effective in reducing Aedes aegypti infestation, which was explained in such a way that it could be implemented by program staff; and a control program with national coverage capable of implementing the proposal. The principal barriers were the complexity of the strategy and the absence of organizational changes needed to facilitate its insertion into the control program. Each barrier or facilitator identified was either static or dynamic in nature. Dynamic factors are those that offer signals for action. Conclusions Multiple barriers and facilitators influence the process of translating community empowerment strategies into the practice of the Cuban Aedes aegypti control program. The analysis of these factors as either static or dynamic makes it possible to design more appropriate and effective strategies that can promote the process and increase the likelihood of success.

Is there a subgroup of long-term evolution among patients with advanced lung cancer?: hints from the analysis of survival curves from cancer registry data.

BACKGROUND: Recently, with the access of low toxicity biological and targeted therapies, evidence of the existence of a long-term survival subpopulation of cancer patients is appearing. We have studied an unselected population with advanced lung cancer to look for evidence of multimodality in survival distribution, and estimate the proportion of long-term survivors. METHODS: We used survival data of 4944 patients with non-small-cell lung cancer (NSCLC) stages IIIb-IV at diagnostic, registered in the National Cancer Registry of Cuba (NCRC) between January 1998 and December 2006. We fitted one-component survival model and two-component mixture models to identify short- and long- term survivors. Bayesian information criterion was used for model selection. RESULTS: For all of the selected parametric distributions the two components model presented the best fit. The population with short-term survival (almost 4 months median survival) represented 64% of patients. The population of long-term survival included 35% of patients, and showed a median survival around 12 months. None of the patients of short-term survival was still alive at month 24, while 10% of the patients of long-term survival died afterwards. CONCLUSIONS: There is a subgroup showing long-term evolution among patients with advanced lung cancer. As survival rates continue to improve with the new generation of therapies, prognostic models considering short- and long-term survival subpopulations should be considered in clinical research.

A multivariate spatio-temporal model for the incidence of imported COVID-19 cases and COVID-19 deaths in Cuba.

To monitor the COVID-19 epidemic in Cuba, data on several epidemiological indicators have been collected on a daily basis for each municipality. Studying the spatio-temporal dynamics in these indicators, and how they behave similarly, can help us better understand how COVID-19 spread across Cuba. Therefore, spatio-temporal models can be used to analyze these indicators. Univariate spatio-temporal models have been thoroughly studied, but when interest lies in studying the association between multiple outcomes, a joint model that allows for association between the spatial and temporal patterns is necessary. The purpose of our study was to develop a multivariate spatio-temporal model to study the association between the weekly number of COVID-19 deaths and the weekly number of imported COVID-19 cases in Cuba during 2021. To allow for correlation between the spatial patterns, a multivariate conditional autoregressive prior (MCAR) was used. Correlation between the temporal patterns was taken into account by using two approaches; either a multivariate random walk prior was used or a multivariate conditional autoregressive prior (MCAR) was used. All models were fitted within a Bayesian framework.

Safety and effectiveness of CIMAvax-EGF administered in community polyclinics.

In spite of the advances in immunotherapy and targeted therapies, lung cancer continues to be the leading cause of cancer-related death. The epidermal growth factor receptor is an established target for non-small cell lung cancer (NSCLC), and its overactivation by the ligands can induce accelerated proliferation, angiogenesis, and metastasis as well as proinflammatory or immunosuppressive signals. CIMAvax-EGF is an epidermal growth factor (EGF)-depleting immunotherapy that is approved for the treatment of NSCLC patients in Cuba. The study was designed as a phase IV trial to characterize the safety and effectiveness of CIMAvax-EGF in advanced NSCLC patients treated in 119 community polyclinics and 24 hospitals. CIMAvax-EGF treatment consisted of four bi-weekly doses followed by monthly boosters. Overall, 741 NSCLC patients ineligible for further cancer-specific treatment were enrolled. CIMAvax-EGF was safe, and the most common adverse events consisted of mild-to-moderate injection site reactions, fever, chills, tremors, and headache. For patients completing the loading doses, the median survival was 9.9 months. For individuals achieving at least stable disease to the frontline and completing vaccination induction, the median survival was 12 months. Most of the functional activities and symptoms evaluated through the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire improved over time. In conclusion, this real-world trial demonstrated that CIMAvax-EGF was safe and effective in patients who were vaccinated in the maintenance scenario. A larger effect was seen in subjects with poor prognosis like those with squamous tumors and high EGF levels. Remarkably, this community-based intervention was very important because it demonstrated the feasibility of treating advanced lung cancer patients with active immunotherapy in primary care institutions. In addition to CIMAvax-EGF, patients received supportive care at the community clinic. Vaccine administration by the family doctors at the polyclinics reduced the patients' burden on the medical oncology services that continued providing chemotherapy and other complex therapies. We conclude that community polyclinics constitute the optimal scenario for administering those cancer vaccines that are safe and require prolonged maintenance in patients with advanced cancer, despite the continuous deterioration of their general condition. Clinical trial registration: https://rpcec.sld.cu/trials/RPCEC00000205-En, identifier RPCEC00000205.

[Low-affinity Fcγ receptor IIa gene polymorphism and dengue bleeding disorder]. / Polimorfismo del receptor FcγRIIa y su posible relación con las manifestaciones clínicas del dengue.

INTRODUCTION: The pathophysiological changes that determine the severity of dengue are still not well known, therefore it is important to study the probable relationship with the host genetic. METHODS: We analyzed the possible association between the FcγRIIa polymorphism and clinical signs in individuals who suffered dengue infection in 2006, using contingency tables. RESULTS: We found that bleeding was significantly associated to FcγRIIa H/H131 genotype (80%). CONCLUSION: Our results suggest that in clinical dengue infection the bleeding could be associated to FcγRIIa H/H131 genotype.

Nimotuzumab Increases the Recovery Rate of Severe and Critical COVID-19 Patients: Evaluation in the Real-World Scenario.

EGFR signaling is an important regulator of SARS-CoV induced lung damage, inflammation and fibrosis. Nimotuzumab is a humanized anti-EGFR antibody registered for several cancer indications. An expanded access study was conducted to evaluate the safety and recovery rate of severe and critical patients with confirmed SARS-CoV-2 infection, treated with nimotuzumab in combination with the standard of care in the real-world scenario. The antibody was administered as an intravenous infusions every 72 h, up to 5 doses. In order to assess the impact of nimotuzumab, the recovery rate was compared with a paired retrospective cohort. Control patients received standard treatment according the national protocol but not nimotuzumab. Overall, 1,151 severe or critical patients received nimotuzumab in 21 hospitals of Cuba. Median age was 65 and 773 patients had at least one comorbidity. Nimotuzumab was very well-tolerated and mild or moderate adverse events were detected in 19 patients. 1,009 controls matching with the nimotuzumab patients, were selected using a "propensity score" method. The 14-day recovery rate of the nimotuzumab cohort was 72 vs. 42% in the control group. Controls had a higher mortality risk (RR 2.08, 95% CI: 1.79, 2.38) than the nimotuzumab treated patients. The attributable fraction was 0.52 (95% CI: 0.44%; 0.58), and indicates the proportion of deaths that were prevented with nimotuzumab. Our preliminary results suggest that nimotuzumab is a safe antibody that can reduce the mortality of severe and critical COVID-19 patients.

COVID-19 and Cancer in Cuba.

The COVID-19 pandemic has called attention to the contribution of comorbidities, including cancer and brought additional challenges to previously existing programs for cancer treatment and control. The COVID-19 pandemic in Cuba was addressed through an integrated all-society action plan that to date has been largely successful with a low incidence of COVID-19 and mortality rates several-fold lower than worldwide averages. Despite downsizing many other health components all oncology services were maintained. Between March 11, when the first case was detected, until July 23, Cuba reported 2,449 cases of COVID-19 that included 28 (1.14%) with a diagnosis of cancer. Distribution among cancer diagnoses did not deviate from that expected according to cancer epidemiology in Cuba. However, although the probability of getting infected with the coronavirus for a cancer patient (0.012%), was not higher than that of the general population (0.020%), 9 of the 28 (32.1%) died, a lethality higher than that of COVID-19 patients without cancer (3.5%) a difference that is statistically significant (P< .001). We argue that going forward scientific research on the relationship of aging, inflammation and cancer, including identification of biomarkers and the development of novel therapeutic interventions, should become one of the priorities in the post-COVID agenda of both oncologists and infectious disease scientists.

Treatment of COVID-19 patients with the anti-CD6 antibody itolizumab.

OBJECTIVES: COVID-19 can lead to a hyperinflammatory state. CD6 is a glycoprotein expressed on mature T lymphocytes which is a crucial regulator of the T-cell activation. Itolizumab is a humanised antibody targeting CD6. Nonclinical and clinical data in autoimmune diseases indicate that it lowers multiple cytokines primarily involving the Th1/Th17 pathway. The primary objective of this study was to assess the impact of itolizumab in arresting the lung function deterioration of COVID-19 patients. Secondary objectives included safety, duration of ventilation, 14-day mortality and evaluation of interleukin 6 concentration. METHODS: Patients with confirmed SARS-CoV-2 received itolizumab in combination with other therapies included in the national protocol for COVID-19. RESULTS: Seventy critical, severe or moderate patients were treated with itolizumab in 10 Cuban hospitals. Median age was 68, and 94% had comorbidities. After 72 h, most patients improved the PO2/FiO2 ratio and reduced FiO2 requirements. Ventilation time was 8 days for critical and 1 day for severe cases. Ten patients had related adverse events while 3 subjects developed related serious events. In 30 patients, interleukin 6 decreased in individuals with high level and did not change in those with lower concentration. Fourteen-day lethality rate was 4% and 18% for moderate and severe patients, respectively. The proportion of moderate or severe patients with ventilation or death at day 14 was 9.8%. Time to treatment, neurological manifestations and biomarkers such as NLR were significantly associated with higher lethality. CONCLUSIONS: The opportune administration of itolizumab might interrupt the hyperinflammatory cascade and prevent COVID-19 morbidity and mortality.

Neutralizing antibody response variation against dengue 3 strains.

To evaluate the neutralizing antibody activity of a human sera panel against seven strains of the homotypic virus. Sera were collected from DENV-3 immune individuals. Two DENV-3 genotypes and strains isolated at different time-points during the 2000 and 2001-2002 Havana epidemics were included. A panel of 20 late convalescent sera collected 16-18 months after acute illness from DF and DHF patients are studied. These individuals were infected during the 2001-2002 Havana DENV-3 epidemic. All but four sera collected from DF cases had a secondary DENV-1/DENV-3 infection. Sera neutralizing antibody titer against the seven DENV-3 strains were determined by plaque reduction neutralization technique. Sera samples were tested simultaneously. Studied sera showed higher levels of neutralizing antibodies to DENV-3 strains of genotype III compared to genotype V. Interesting, higher levels of neutralizing antibodies were detected to DENV-3 strain isolated at the end of the epidemic 2001-2002. An increased tendency of GMT of neutralizing antibodies according to epidemic evolution was observed for the 2001-2002 outbreak. In general, antibody levels in sera collected from DF cases were higher. Differences in the neutralization capacity of immune DENV-3 sera tested against two homologous genotypes including strains of the same genotype are demonstrated. Observed results suggest that virus changed in the course of the epidemic. The implications of this finding in terms of dengue pathogenesis and vaccine development need to be considered.

Validation of Instruments for Assessing Drug Safety Management During the Conduction of Clinical Trials.

BACKGROUND: The management of drug safety with the collection of reliable safety data during the conduction of clinical trials conduct is essential for the registry and marketing of products. The systematic evaluation of this process, based on objective measures, requires the application of quality instruments. This study was aimed to design and validate eight instruments through the components of quality (structure, process, and results), for characterizing and assessing the process of drug safety management, during the conduction of clinical trials. METHODS: The eight instruments were designed according to the international recommendations for Good Clinical Practice (GCP) and comprise a knowledge survey for professionals at the investigational sites, a satisfaction scale of internal and external clients and a satisfaction survey for patients with the treatment of the adverse events. The instruments also include a checklist to evaluate the safety management infrastructure (human, material and organizational resources) in the sponsoring center, a checklist to evaluate the same criterion at the investigational sites and three checklists that evaluate adherence to regulatory requirements of essential documents (investigator's brochure, protocol, and informed consent form). The content validity was evaluated by Delphi method and the reliability was determined by Cronbach α test. RESULTS: All the items were valued as very adequate after the second round of the expert panel. The instruments were deemed as appropriate and understandable in the pre-test performed. All responders agreed with the options given and the accessibility of the application. Only 10% of professionals at the research sites suggested that the knowledge survey was too long. Cronbach α values between .66 and .93 were obtained. CONCLUSION: The structure, process, and outcome framework allowed for the characterization of drug safety management during clinical trials, providing a useful approach for the promoter to systematically measure and evaluate the process. The eight instruments were deemed as reliable, feasible and easy to be used for examining drug safety management while carrying out clinical trials.

Differential effects of two therapeutic cancer vaccines on short- and long-term survival populations among patients with advanced lung cancer.

BACKGROUND: Progress in immunotherapy has revolutionized the treatment landscape for advanced lung cancer, with emerging evidence of patients experiencing long-term survivals. The goal of this study was to explore the existence of short- and long-term survival populations and to assess the effect of immunotherapy on them. METHODS: Data from two randomized, multicenter, controlled clinical trials was used to evaluate the effect of two therapeutic vaccines (anti-idiotypic vaccine VAXIRA and anti-EGF vaccine CIMAVAX) on survival curves in advanced non-small cell lung cancer patients. Data were fitted to Kaplan-Meier, standard Weibull survival, and two-component Weibull mixture models. Bayesian Information Criterion was used for model selection. RESULTS: VAXIRA did not modify, neither the fraction of patients with long-term survivals (0.18 in the control group v 0.19 with VAXIRA, P = .88), nor the median overall survival of the patients in the short-term survival subpopulation (6.8 v 7.8 months, P = .24). However, this vaccine showed great benefit for the patients belonging to the subpopulation of patients with long-term survival (33.8 v 76.6 months, P <.0001). CIMAVAX showed impact in the overall survival of both short- and long-term populations (6.8 v 8.8 months, P = .005 and 33.8 v 61.8 months, P = .007). It also increased the proportion of patients with long-term survival (from 0.18 to 0.28, P = .02). CONCLUSIONS: This study shows that therapeutic vaccines produce differential effects on short- and long-term survival populations and illustrates the application of advanced statistical methods to deal with the long-term evolution of patients with advanced lung cancer in the era of immunotherapy.

Overall Survival of Patients with Locally Advanced or Metastatic Esophageal Squamous Cell Carcinoma Treated with Nimotuzumab in the Real World.

INTRODUCTION: Despite improvements in surgical techniques and treatments introduced into clinical practice, the overall survival of patients with esophageal squamous cell carcinoma remains low. Several epidermal growth factor receptor inhibitors are being evaluated in the context of clinical trials, but there is little evidence of effectiveness in real-world conditions. This study aimed at assessing the effectiveness of nimotuzumab combined with onco-specific treatment in Cuban real-life patients with locally advanced or metastatic esophageal squamous cell carcinoma. METHODS: A comparative and retrospective effectiveness study was performed. The 93 patients treated with nimotuzumab were matched, with use of propensity score matching, with patients who received a diagnosis of locally advanced or metastatic squamous cell carcinoma of the esophagus in three Cuban provinces reported between 2011 and 2015 to the National Cancer Registry. The Kaplan-Meier method was used to estimate event-time distributions. Log-rank statistics were used for comparisons of overall survival between groups. A two-component mixture model assuming a Weibull distribution was fitted to assess the effect of nimotuzumab on short-term and long-term survival populations. RESULTS: There was an increase in median overall survival in patients treated with nimotuzumab (11.9 months versus 6.5 months without treatment) and an increase in the 1-year survival rate (54.0% versus 21.9% without treatment). The 2-year survival rates were 21.1% for patients treated with nimotuzumab and 0% in the untreated cohort. There were statistically significant differences in survival between groups treated and not treated with nimotuzumab, both in the short-term survival population (6.0 months vs 4.0 months, p = 0.009) and in the long-term survival population (18.0 months vs 11.0 months, p = 0.001). CONCLUSIONS: Our study shows that nimotuzumab treatment concurrent with chemoradiotherapy increases the survival of real-world patients with locally advanced or metastatic esophageal squamous cell carcinoma. Further prospective studies are required to confirm the therapeutic effectiveness of nimotuzumab in esophageal cancer.

Intranasal immunisation with a 62 kDa proteinase combined with cholera toxin or CpG adjuvant protects against Trichomonas vaginalis genital tract infections in mice.

Trichomonosis, caused by the protozoan parasite Trichomonas vaginalis, is one of the most frequent sexually transmitted diseases and is widely spread in all continents. Trichomonas vaginalis as well as other protozoan organisms have high levels of proteolitic activity mainly of the cysteine-proteinase type. This activity is necessary for recognition and adhesion of the parasite to the superficial epithelial cells of the host. In the present study, we show that intranasal immunisation with a 62 kDa cysteine-proteinase purified from T. vaginalis excretion-secretion products in combination with cholera toxin or with synthetic oligodeoxynucleotides (ODN) that contain unmethylated CpG motifs (CpG-ODN) elicits 62kDa specific IgG and IgA in vaginal lavage fluid and specific IgG in serum. This immunisation protocol resulted in enhanced elimination of parasites following intravaginal challenge of BALB/c mice.

Prospective, comprehensive, and effective viral monitoring in Cuban children undergoing solid organ transplantation.

PURPOSE: In Cuba, viral monitoring in the post-transplant period was not routinely performed. The aim of this research is to identify the most frequent viruses that affect transplanted Cuban children, by implementing a viral follow-up during the post-transplant period. METHODS: The study population included all Cuban pediatric patients who underwent solid organ transplantation (SOT) between November 2009 and December 2012. A total of 34 transplanted pediatric patients of kidney (n = 11) and liver (n = 23) were prospectively monitored during a 34-week period for viral DNAemia and DNAuria by simultaneous detection of cytomegalovirus (CMV), Epstein-Barr virus, herpes simplex virus type 1 and 2, varicella zoster virus, human herpesvirus 6, human adenovirus, and polyomaviruses (BKV and JCV) using quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: Viral genome of at least one virus was detected in 21 of 34 recipients, 18 patients excreted virus in urine while 12 presented DNAemia. CMV (41.2%) and BKV (35.3%) were the most frequent viruses detected during the follow-up. CMV was the virus mainly associated with clinical symptoms and DNAemia. Its excretion in urine (with cut off value of 219 copies/mL) was associated with detection in plasma (p < 0.001); furthermore, CMV viruria was predictive of CMV viremia (OR:8.4, CI:2.4-29.1, p = 0.001). There was no association between high viral load and clinical complications, due to the prompt initiation of preemptive ganciclovir. CONCLUSION: This comprehensive viral monitoring program effectively prevents the development of critical viral disease, thus urge the implementation of qRT-PCR as routine for viral monitoring of transplanted Cuban organ recipients.

The relationship between economic status, knowledge on dengue, risk perceptions and practices.

The reemergence of dengue as an important public health problem reflects the difficulties in sustaining vertically organized, effective, control programs and the need for community-based strategies for Aedes aegypti control that result in behavioral change. We aimed to disentangle the relationships between underlying determinants of dengue related practices. We conducted a cross-sectional study in 780 households in La Lisa, Havana, Cuba. A questionnaire and an observation guide were administrated to collect information on variables related to economic status, knowledge on dengue, risk perception and practices associated with Aedes aegypti breading sites. To test a conceptual model that hypothesized direct relationships among all these constructs, we first used Exploratory Factor Analysis with Principal Component Analysis to establish the relationship between observed variables and the underlying latent variables. Subsequently, we tested whether the observed data supported the conceptual model through Confirmatory Factor Analysis. Exploratory Factor Analysis indicated that the items measured could be reduced into five factors with an eigenvalue >1.0: Knowledge on dengue, Intradomiciliar risk practices, Peridomiciliar risk practices, Risk perception and Economic status. The proportion of the total variance in the data explained by these five factors was 74.3%. The Confirmatory Factor Analysis model differed from our hypothesized conceptual model. Only Knowledge on dengue had a significant, direct, positive, effect on Practices. There was also a direct association of Economic status with Knowledge on dengue, but not with Risk perception and Practices. Clarifying the relationship between direct and indirect determinants of dengue related practices contributes to a better understanding of the potential effect of Information Education and Communication on practices and on the reduction of Aedes aegypti breeding sites and provides inputs for designing a community based strategy for dengue control.

Prevalence of antibodies to Borrelia burgdorferi sensu stricto in humans from a Cuban village.

UNLABELLED: Lyme disease has not been officially reported in Cuba. However, clinical cases have been serologically reported. Seroprevalence survey of Borrelia burgdorferi sensu stricto antibodies in humans in the country has not been conducted. OBJECTIVE: To estimate the prevalence of borrelial antibodies in inhabitants of a village with historically high level of tick infestation. METHODS: Serum specimens from 247 persons randomly selected from the population of the village were examined by IgG Western blot using B31 strain for estimating the prevalence of antibodies profile. RESULTS: A seroprevalence value interval (95% CI) of 0.6%-7.2% was estimated for the studied population. The prevalent borrelial protein bands on immunoblots were 41, 72, 90/93, 34, 47, 60, 58, 56, 65/66 and 31 kDa in a decreasing order of significance. CONCLUSION: These results support the previous serological findings, suggesting the presence of this borreliosis in Cuba.

Testing the effectiveness of community-based dengue vector control interventions using semiparametric mixed models.

OBJECTIVE: To evaluate the results obtained though intersectoral coordination and community empowerment in one study carried out during 6 years in Playa Municipality, Cuba. METHODS: A longitudinal assessment comparing one intervention and one control area was conducted. The intervention encompasses two main stages separated by two dengue outbreaks. The first stage, focused on strengthening intersectoral coordination, was initiated in January 2000. In August 2003, a complementary strategy, focused on community empowerment and was initiated in half of the intervention area. In the control area, routine dengue control activities continued without additional input. We used entomologic surveillance data from January 1999 to December 2005 to assess the effectiveness. We computed the Breteau index (BI) per health area and the 95% confidence interval for the difference between the BIs at each time point. A semiparametric mixed model to capture the evolution in time of Aedes aegypti larval densities was fitted. RESULTS: The BI in the control area showed the lowest value before starting the intervention. This was reversed 1 year after launching intersectoral activities for dengue control in the intervention area. In spite of spraying actions in all areas, the differences in BI between intervention and control areas remain significant until December 2002. Although for the next 2 years no differences were observed, they become significant again in December 2004, which corresponds with the implementation of the complementary community-based vector control strategy in the intervention area. CONCLUSIONS: The model fitted identified monotonous trends over time and reversal trends at particular moments. The confidence bands indicate sections with significant differences between areas. Our data increase the evidence that the intersectoral coordination and community empowerment strategy for A. aegypti control is effective.