Zika and Dengue Interactions in the Context of a Large Dengue Vaccine Clinical Trial in Latin America.

A phase III dengue vaccine trial including 9- to 16-year-olds in Latin America (NCT01374516) was ongoing at the time of a Zika outbreak. We explored interactions between dengue and Zika, in the context of dengue vaccination. Symptomatic virologically confirmed Zika (VCZ) was evaluated using acute-phase sera from febrile participants (January 2013-March 2018). Neutralizing antibody geometric mean titers (GMTs) were evaluated pre- and post-Zika outbreak (months 25 and 72) in 2,000 randomly selected participants. Baseline dengue serostatus was determined using the plaque reduction neutralization test or inferred post hoc using nonstructural protein 1 IgG ELISA at M13 (case-cohort analysis). Vaccine efficacy against VCZ and serologically suspected Zika (SSZ) was estimated. Overall, 239/10,157 (2.4%) acute-phase samples were VCZ positive during the study. Dengue vaccine efficacy against VCZ was 27.8% (95% CI: 0.3; 47.7) among baseline dengue-seropositive participants. No vaccine effect was evident against SSZ. Zika antibody GMTs increased from pre- to post-Zika epidemic, with smaller increases observed for participants who were dengue seropositive at baseline than for those who were dengue seronegative: post-/pre-Zika GMT ratios for baseline dengue-seropositive participants were 21.5 (vaccine group) and 30.8 (placebo); and for dengue seronegatives, 88.1 and 89.5, respectively. Dengue antibody GMTs post-Zika were higher in dengue vaccine and placebo recipients with SSZ than those without SSZ in both dengue seropositives and seronegatives. Dengue vaccine did not enhance symptomatic Zika illness in dengue-seropositive individuals, rather it reduced the risk of VCZ. Zika infection boosted preexisting vaccine-induced or naturally occurring dengue-neutralizing antibodies.

Immune Response Persistence and Safety of a Booster Dose of the Tetravalent Dengue Vaccine in Adolescents and Adults Who Previously Completed the 3-dose Schedule 4-5 Years Earlier in Latin America: A Randomized Placebo-controlled Trial.

BACKGROUND: We previously described an increased immune response 28 days after a booster dose of the live, attenuated, tetravalent dengue vaccine (CYD-TDV) in healthy adolescents and adults in Latin America (CYD64, NCT02623725). This follow-up study evaluated immune response persistence and safety of a CYD-TDV booster dose up to Month (M) 24 post-booster. METHODS: This study included 250 participants who previously received 3 primary doses of CYD-TDV in the CYD13 (NCT00993447) and CYD30 (NCT01187433) studies, and who were randomized 4-5 years later to receive a CYD-TDV booster or placebo (3:1). Dengue neutralizing antibodies against the parental dengue virus strains were assessed using the plaque reduction neutralization test (PRNT50) at M6, M12, and M24 post-booster. Post-booster memory B-cell responses were assessed in a subset of participants using the FluoroSpot assay up to M12 post-booster. RESULTS: In the CYD-TDV group (n = 187), dengue neutralizing antibody geometric mean titers (GMTs) declined from the peak at day 28 through to M24 for all serotypes. GMTs at M24 were similar to those at pre-booster among baseline dengue seropositives. A similar trend was observed for baseline dengue seronegatives, albeit at a lower magnitude. Previous vaccination-induced detectable B-cell memory responses in seropositives and seronegatives that decreased to pre-booster levels at M12 post-booster. The CYD-TDV booster dose was well-tolerated. CONCLUSIONS: In baseline dengue seropositives, following a CYD-TDV booster dose administered 4-5 years after primary immunization, dengue neutralizing antibody GMTs and B-cell memory responses peaked in the short-term before gradually decreasing over time. A CYD-TDV booster dose could improve protection against dengue during outbreak periods.

Evaluation of dengue serological tests available in Puerto Rico for identification of prior dengue infection for prevaccination screening.

We assessed a dengue IgG rapid diagnostic test (RDT) and IgG enzyme-linked immunosorbent assay (ELISA) to determine their suitability for dengue prevaccination screening. Each exhibited ≥99% specificity. The RDT demonstrated no Zika cross-reactivity, while the ELISA displayed greater sensitivity. Both could safely guide vaccination in Puerto Rico pending availability of improved serotests.

Antiretroviral drug resistance in HIV-infected patients in Colombia.

BACKGROUND: Systematically obtained data on antiretroviral (ARV) resistance in Colombia are lacking. Local estimates of resistance are needed to guide testing, therapy, and policy. METHODS: A cross-sectional study was performed in ARV-naïve individuals and in patients with first ARV failure. Genotypic resistance testing was performed using Viro-seq. Predicted success to first- and second-line regimens recommended by the Colombian HIV treatment guidelines was estimated. RESULTS: One hundred and three naïve and 77 experienced patients were included. For naïve patients, resistance mutations were detected in 5.8%, with the most common mutations being 103N (n=5; 4.9%) and 184V (n=3; 2.9%). CD4 count <200cells/mm(3) (p=0.04) and Centers for Disease Control and Prevention (CDC) category C (p=0.004) were associated with primary resistance. For experienced individuals, regimens were non-nucleoside reverse transcriptase inhibitor (NNRTI)-based in 57.1%, protease inhibitor (PI)-based in 14.3%, boosted PI-based in 26.0%, and nucleoside reverse transcriptase inhibitor (NRTI)-based in 2.6% of the cases. Resistance mutations were found in 66 patients (85.7%) with failure. The most common mutations were 184V (n=48; 62.3%), 103N (n=37; 48.1%), G190A/S (n=9; 11.7%), and L90M (n=9; 11.7%). Twelve percent had thymidine analogue mutations (TAMs) but only 1% had more than 1 TAM. The predicted success of regimens recommended by the Colombian guidelines was 95% for naïve patients and 84% for experienced patients. Genotyping could increase the success rates to 100% and 94%, respectively. CONCLUSIONS: The frequency of primary HIV resistance in Colombia is similar to estimates from other countries in Latin America. CD4 count and CDC category C may allow identification of most of the naïve patients who would benefit from resistance testing. Resistance testing could favorably impact therapy modification in about 5% and 10% of naïve and experienced patients, respectively.

An outbreak of Candida spp. bloodstream infection in a tertiary care center in Bogotá, Colombia

Several cases of Candida bloodstream infections were documented from June to October 2004 at a tertiary care center in Bogotá, Colombia. Since no cases of candidemia had occurred during the preceding four months, an outbreak was declared. As a result, a microbiological study, a revision of infection control practices and a case-control study were performed. In all, 18 cases of candidemia were ascertained. Parenteral nutrition (p=0.04), presence of a central line (p=0.03), and severity of illness (p=0.03) were associated with candidemia in bivariate analysis. Diverse Candida species were observed. Candida parapsilosis contamination was found in plastic containers used for transient intravenous (IV) medication storage at the bedside, plastic bags reused for the transportation of IV medicines and cotton used for disinfection of IV ports. Poor infection control practices were widely observed. The outbreak was controlled after elimination of plastic bags used for transportation, instauration of daily disinfection of IV medication containers, acquisition of sterile alcohol swabs for port disinfection and staff education. It was concluded that candidemia was associated with previously-described risk factors and that poor infection-control practices were likely responsible for the outbreak.

An outbreak of Candida spp. bloodstream infection in a tertiary care center in Bogotá, Colombia.

Several cases of Candida bloodstream infections were documented from June to October 2004 at a tertiary care center in Bogotá, Colombia. Since no cases of candidemia had occurred during the preceding four months, an outbreak was declared. As a result, a microbiological study, a revision of infection control practices and a case-control study were performed. In all, 18 cases of candidemia were ascertained. Parenteral nutrition (p=0.04), presence of a central line (p=0.03), and severity of illness (p=0.03) were associated with candidemia in bivariate analysis. Diverse Candida species were observed. Candida parapsilosis contamination was found in plastic containers used for transient intravenous (IV) medication storage at the bedside, plastic bags reused for the transportation of IV medicines and cotton used for disinfection of IV ports. Poor infection control practices were widely observed. The outbreak was controlled after elimination of plastic bags used for transportation, instauration of daily disinfection of IV medication containers, acquisition of sterile alcohol swabs for port disinfection and staff education. It was concluded that candidemia was associated with previously-described risk factors and that poor infection-control practices were likely responsible for the outbreak.

Rate and predictors of optimal virologic response to antiretroviral therapy in Colombia.

OBJECTIVE: To estimate the rate of optimal response to antiretroviral therapy and its predictors in Colombia. METHODS: A retrospective cohort study was performed. The medical records of all patients at three major HIV clinics in different areas of Colombia, South America, were reviewed. Eligible patients met the following criteria: (1) viral load test available while on therapy; and (2) patients must have been on a stable first antiviral regimen for at least 1 year (48 weeks). Optimal virologic response was defined as a viral load <400 copies/ml. RESULTS: Two hundred and twenty patients were eligible for the study. The optimal virologic response rate was 40% (95% confidence interval 34-46%). Younger age (p=0.02) and western region of the country (p=0.026) were the only significant predictors of non-optimal response in bivariate analysis. Multivariate logistic regression analysis confirmed younger age (p=0.0054) and geographic area (p=0.0468) as independent predictors of non-optimal response. CONCLUSIONS: The optimal response rate in some areas of Colombia seems lower than that reported for other areas of the developing world. Poorer virologic responses were observed in younger patients and in those from the western region of the country.

[Correlation and concordance of three HIV viral load techniques available in Colombia]. / Correlación y concordancia de tres técnicas de cuantificación de carga viral del VIH disponibles en Colombia.

OBJECTIVE: To compare the performance of three available technologies for Human Immunodeficiency Virus quantitation in Colombia. METHODS: Samples from different areas of the Country were selected by convenience and underwent Human Immunodeficiency Virus quantitation using three methods: Versant bDNA 3.0 (Bayer), LCx HIV (Abbott) and Amplicor Monitor v1.5 (Roche). All samples were processed at the Centro de Análisis Molecular in Bogotá, Colombia. Results obtained with the three techniques were compared using linear regression. Additionally, the concordance between techniques was assessed calculating the unweighted kappa, the frequency of discordance according to cut-off points of clinical importance, and the frequency of differences exceeding 0.5 logs. RESULTS: The correlation between techniques was highly significant, with an R2 higher than 0.97. The concordance was substantial, with unweighted kappas above 0.7. Nevertheless, the frequency of discordance for cut-off points of clinical importance and the frequency of differences exceeding 0.5 logs were considerable (8.8%-15.6% and 19.6%-36.3% respectively). CONCLUSION: The three technologies for quantitation of viral load are adequate with high levels of correlation and concordance. However, because of the observed variability we recommend comparing a reading from one technique with another reading from the same technique when incorporating the results into clinical decision making.

The use of endocervical curettage in women with low-grade squamous intraepithelial lesions or atypical squamous cells of unknown significance on Pap smear.

OBJECTIVE: To determine the use of endocervical curettage in women with low-grade squamous intraepithelial lesions (LSIL) or atypical squamous cells of unknown significance (ASCUS) on Pap smear. METHODS: A cross-sectional study evaluated women at a single center colposcopy service between January 1999 and December 2003 having LSIL or ASCUS on Pap smear and compatible lesions on colposcopic examination who underwent endocervical curettage. Associations of abnormal endocervical curettage results with lesion topography, age, and satisfactory colposcopy were evaluated. A multivariate logistic regression model was used to evaluate independent associations and estimate the probabilities of abnormal endocervical curettage for different clinical scenarios. RESULTS: Two hundred thirty-seven women were included. The estimated prevalence of abnormal endocervical curettage was 5.5% (95% CI = 2.6%-8.3%). Only 2 endocervical curettage results reported cervical intraepithelial neoplasia 2 or 3 (0.8%, 95% CI = 0%-2%). Bivariate analysis showed a significant association between abnormal endocervical curettage result and central topography of the lesion (p = .01). A multivariate logistic regression analysis confirmed that association (p = .04). The model was used to calculate probabilities of abnormal results in different scenarios. CONCLUSIONS: The overall prevalence of abnormal endocervical curettage in patients with LSIL or ASCUS on Pap smear is low. The prevalence of endocervical curettage results reporting cervical intraepithelial neoplasia 2 or 3 lesions is even lower. Therefore, the use of systematic endocervical curettage performance in this setting is questionable. Our model helps to predict the probability of abnormal results and assist in the decision of whether to perform endocervical curettage.