Combining Google Earth and GIS mapping technologies in a dengue surveillance system for developing countries

<p>Abstract</p> <p>Background</p> <p>Dengue fever is a mosquito-borne illness that places significant burden on tropical developing countries with unplanned urbanization. A surveillance system using Google Earth and GIS mapping technologies was developed in Nicaragua as a management tool.</p> <p>Methods and Results</p> <p>Satellite imagery of the town of Bluefields, Nicaragua captured from Google Earth was used to create a base-map in ArcGIS 9. Indices of larval infestation, locations of tire dumps, cemeteries, large areas of standing water, etc. that may act as larval development sites, and locations of the homes of dengue cases collected during routine epidemiologic surveying were overlaid onto this map. Visual imagery of the location of dengue cases, larval infestation, and locations of potential larval development sites were used by dengue control specialists to prioritize specific neighborhoods for targeted control interventions.</p> <p>Conclusion</p> <p>This dengue surveillance program allows public health workers in resource-limited settings to accurately identify areas with high indices of mosquito infestation and interpret the spatial relationship of these areas with potential larval development sites such as garbage piles and large pools of standing water. As a result, it is possible to prioritize control strategies and to target interventions to highest risk areas in order to eliminate the likely origin of the mosquito vector. This program is well-suited for resource-limited settings since it utilizes readily available technologies that do not rely on Internet access for daily use and can easily be implemented in many developing countries for very little cost.</p

Effect of rAd5-Vector HIV-1 Preventive Vaccines on HIV-1 Acquisition: A Participant- Level Meta-Analysis of Randomized Trial

Background Three phase 2b, double-blind, placebo-controlled, randomized efficacy trials have tested recombinant Adenovirus serotype-5 (rAd5)-vector preventive HIV-1 vaccines: MRKAd5 HIV-1 gag/pol/nef in Step and Phambili, and DNA/rAd5 HIV-1 env/gag/pol in HVTN505. Due to efficacy futility observed at the first interim analysis in Step and HVTN505, participants of all three studies were unblinded to their vaccination assignments during the study but continued follow–up. Rigorous meta-analysis can provide crucial information to advise the future utility of rAd5-vector vaccines. Methods We included participant-level data from all three efficacy trials, and three Phase 1–2 trials evaluating the HVTN505 vaccine regimen. We predefined two co-primary analysis cohorts for assessing the vaccine effect on HIV-1 acquisition. The modified-intention-to-treat (MITT) cohort included all randomly assigned participants HIV-1 uninfected at study entry, who received at least the first vaccine/placebo, and the Ad5 cohort included MITT participants who received at least one dose of rAd5-HIV vaccine or rAd5-placebo. Multivariable Cox regression models were used to estimate hazard ratios (HRs) of HIV-1 infection (vaccine vs. placebo) and evaluate HR variation across vaccine regimens, time since vaccination, and subgroups using interaction tests. Findings Results are similar for the MITT and Ad5 cohorts; we summarize MITT cohort results. Pooled across the efficacy trials, over all follow-up time 403 (n = 224 vaccine; n = 179 placebo) of 6266 MITT participants acquired HIV-1, with a non-significantly higher incidence in vaccine recipients (HR 1.21, 95% CI 0.99–1.48, P = 0.06). The HRs significantly differed by vaccine regimen (interaction P = 0.03; MRKAd5 HR 1.41, 95% CI 1.11–1.78, P = 0.005 vs. DNA/rAd5 HR 0.88, 95% CI 0.61–1.26, P = 0.48). Results were similar when including the Phase 1–2 trials. Exploratory analyses based on the efficacy trials supported that the MRKAd5 vaccine-increased risk was concentrated in Ad5-positive or uncircumcised men early in follow-up, and in Ad5-negative or circumcised men later. Overall, MRKAd5 vaccine-increased risk was evident across subgroups except in circumcised Ad5-negative men (HR 0.97, 95% CI 0.58−1.63, P = 0.91); there was little evidence that the DNA/rAd5 vaccine, that was tested in this subgroup, increased risk (HR 0.88, 95% CI 0.61–1.26, P = 0.48). When restricting the analysis of Step and Phambili to follow-up time before unblinding, 114 (n = 65 vaccine; n = 49 placebo) of 3770 MITT participants acquired HIV-1, with a non-significantly higher incidence in MRKAd5 vaccine recipients (HR 1.30, 95% CI 0.89–1.14, P = 0.18). Interpretation and Significance The data support increased risk of HIV-1 infection by MRKAd5 over all follow-up time, but do not support increased risk of HIV-1 infection by DNA/rAd5. This study provides a rationale for including monitoring plans enabling detection of increased susceptibility to infection in HIV-1 at-risk populations

HIV Prevention in High-Risk Women in South Africa: Condom Use and the Need for Change

INTRODUCTION: Young women are at disproportionate risk of HIV infection in South Africa. Understanding risk behaviors and factors associated with ability to negotiate safe sex and condom use is likely to be key in curbing the spread of HIV. Traditionally prevention efforts have focused on creating behavioral changes by increasing knowledge about HIV/AIDS. METHODS: This was a cross-sectional analysis from a prospective observational cohort study of 245 women at a high-risk of HIV infection in KwaZulu-Natal, South Africa. RESULTS: Participants demonstrated a high level of HIV/AIDS knowledge. Overall, 60.3% of participants reported condom use. Reported condom use at last sexual encounter varied slightly by partner type (57.0% with steady versus 64.4% with casual partners), and self-perceived ability to choose to use a condom was significantly lower with steady partners compared to casual partners (p<0.01). In multivariate analysis, women who had high school education were more likely to use condoms at their last sex encounter compared to those with only primary school education (RR of 1.36 (95% Confidence Interval (CI) 1.06-1.75) and 1.46 (95% CI 1.13-1.88) for grades 8-10 and 11-12, respectively). Those who used condoms as a contraceptive method were twice as likely to use condoms compared to women who did not report using them as a contraceptive method. Greater perceived ability to choose to use condoms was associated with higher self-reported condom use at last encounter, irrespective of partner type (RR = 2.65 (95% CI 2.15-32.5). DISCUSSION: Self-perceived ability to use condoms, level of formal education and condom use as a contraceptive were all significantly associated with self-reported condom use at last sexual encounter. These findings suggest that that gender inequality and access to formal education, as opposed to lack of HIV/AIDS knowledge, prevent safer sexual practices in South Africa

Prevalence of metabolic syndrome among HIV-positive and HIV-negative populations in sub-Saharan Africa-a systematic review and meta-analysis

BACKGROUND: Metabolic syndrome (MetS) is a constellation of conditions that increase the risk of cardiovascular diseases. It is an emerging concern in sub-Saharan African (SSA) countries, particularly because of an increasingly aging population and lifestyle changes. There is an increased risk of MetS and its components among people living with Human immune deficiency syndrome (HIV) individuals; however, the prevalence of metabolic syndrome in the SSA population and its differential contribution by HIV status is not yet established. This systematic review and meta-analysis were conducted to estimate the pooled prevalence of metabolic syndrome in people living with HIV and uninfected populations, its variation by sub-components. METHODS: We performed a comprehensive search on major databases-MEDLINE (PubMed), EBSCOhost, and Cochrane Database of Systematic Reviews and Web of sciences for original epidemiological research articles that compared proportions of the MetS and its subcomponents between people living with HIV and uninfected patients and published between January 1990-December 2017. The inclusion criteria were adults aged ≥ 18 years, with confirmed HIV status. We assessed the risk of bias using a prevalence studies tool, and random effect meta-analyses were used to compute the pooled overall prevalence. RESULTS: A total of four cross-sectional studies comprising 496 HIV uninfected and 731 infected participants were included in the meta-analysis. The overall prevalence of MetS among people living with HIV was 21.5% (95% CI 15.09-26.86) versus uninfected 12.0% (95% CI 5.00-21.00%), with substantial heterogeneity. The reported relative risk estimate for MetS among the two groups was twofold (RR 1.83, 95% CI 0.98-3.41), with an estimated predictive interval of 0.15 to 22.43 and P = 0.055 higher for the infected population. Hypertension was the most prevalent MetS sub-components, with diverse proportions of people living with HIV (5.2-50.0%) and uninfected (10.0-59.0%) populations. CONCLUSIONS: The high range of MetS prevalence in the HIV-infected population compared to the uninfected population highlights the possible presence of HIV related drivers of MetS. Also, the reported high rate of MetS, irrespective of HIV status, indicates a major metabolic disorder epidemic that requires urgent prevention and management programs in SSA. Similarly, in the era of universal test and treat strategy among people living with HIV cohorts, routine check-up of MetS sub-components is required in HIV management as biomarkers. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016045727

Soluble and Cell-Associated Insulin Receptor Dysfunction Correlates with Severity of HAND in HIV-Infected Women

Blood sugar metabolism abnormalities have been identified in HIV-infected individuals and associated with HIV-associated neurocognitive disorders (HAND). These abnormalities may occur as a result of chronic HIV infection, long-term use of combined antiretroviral treatment (CART), aging, genetic predisposition, or a combination of these factors, and may increase morbidity and mortality in this population.To determine if changes in soluble and cell-associated insulin receptor (IR) levels, IR substrate-1 (IRS-1) levels, and IRS-1 tyrosine phosphorylation are associated with the presence and severity of HAND in a cohort of HIV-seropositive women.This is a retrospective cross-sectional study using patient database information and stored samples from 34 HIV-seropositive women and 10 controls without history of diabetes from the Hispanic-Latino Longitudinal Cohort of Women. Soluble IR subunits [sIR, ectodomain (α) and full-length or intact (αβ)] were assayed in plasma and CSF samples by ELISA. Membrane IR levels, IRS-1 levels, and IRS-1 tyrosine phosphorylation were analyzed in CSF white cell pellets (WCP) using flow cytometry. HIV-seropositive women had significantly increased levels of intact or full-length sIR in plasma (p<0.001) and CSF (p<0.005) relative to controls. Stratified by HAND, increased levels of full-length sIR in plasma were associated with the presence (p<0.001) and severity (p<0.005) of HAND. A significant decrease in IRS-1 tyrosine-phosphorylation in the WCP was also associated with the presence (p<0.02) and severity (p<0.02) of HAND.This study provides evidence that IR secretion is increased in HIV-seropositive women, and increased IR secretion is associated with cognitive impairment in these women. Thus, IR dysfunction may have a role in the progression of HAND and could represent a biomarker for the presence and severity of HAND

Rapid Development of an Integrated Network Infrastructure to Conduct Phase 3 COVID-19 Vaccine Trials

Importance: The COVID-19 pandemic has caused millions of infections and deaths and resulted in unprecedented international public health social and economic crises. As SARS-CoV-2 spread across the globe and its impact became evident, the development of safe and effective vaccines became a priority. Outlining the processes used to establish and support the conduct of the phase 3 randomized clinical trials that led to the rapid emergency use authorization and approval of several COVID-19 vaccines is of major significance for current and future pandemic response efforts. Observations: To support the rapid development of vaccines for the US population and the rest of the world, the National Institute of Allergy and Infectious Diseases established the COVID-19 Prevention Network (CoVPN) to assist in the coordination and implementation of phase 3 efficacy trials for COVID-19 vaccine candidates and monoclonal antibodies. By bringing together multiple networks, CoVPN was able to draw on existing clinical and laboratory infrastructure, community partnerships, and research expertise to quickly pivot clinical trial sites to conduct COVID-19 vaccine trials as soon as the investigational products were ready for phase 3 testing. The mission of CoVPN was to operationalize phase 3 vaccine trials using harmonized protocols, laboratory assays, and a single data and safety monitoring board to oversee the various studies. These trials, while staggered in time of initiation, overlapped in time and course of conduct and ultimately led to the successful completion of multiple studies and US Food and Drug Administration-licensed or -authorized vaccines, the first of which was available to the public less than 1 year from the discovery of the virus. Conclusions and Relevance: This Special Communication describes the design, geographic distribution, and underlying principles of conduct of these efficacy trials and summarizes data from 136 382 prospectively followed-up participants, including more than 2500 with documented COVID-19. These successful efforts can be replicated for other important research initiatives and point to the importance of investments in clinical trial infrastructure integral to pandemic preparedness

Activity and Interactions of Liposomal Antibiotics in Presence of Polyanions and Sputum of Patients with Cystic Fibrosis

BACKGROUND:To compare the effectiveness of liposomal tobramycin or polymyxin B against Pseudomonas aeruginosa in the Cystic Fibrosis (CF) sputum and its inhibition by common polyanionic components such as DNA, F-actin, lipopolysaccharides (LPS), and lipoteichoic acid (LTA). METHODOLOGY:Liposomal formulations were prepared from a mixture of 1,2-Dimyristoyl-sn-Glycero-3-Phosphocholine (DMPC) or 1,2-Dipalmitoyl-sn-Glycero-3-Phosphocholine (DPPC) and Cholesterol (Chol), respectively. Stability of the formulations in different biological milieus and antibacterial activities compared to conventional forms in the presence of the aforementioned inhibitory factors or CF sputum were evaluated. RESULTS:The formulations were stable in all conditions tested with no significant differences compared to the controls. Inhibition of antibiotic formulations by DNA/F-actin and LPS/LTA was concentration dependent. DNA/F-actin (125 to 1000 mg/L) and LPS/LTA (1 to 1000 mg/L) inhibited conventional tobramycin bioactivity, whereas, liposome-entrapped tobramycin was inhibited at higher concentrations--DNA/F-actin (500 to 1000 mg/L) and LPS/LTA (100 to 1000 mg/L). Neither polymyxin B formulation was inactivated by DNA/F-actin, but LPS/LTA (1 to 1000 mg/L) inhibited the drug in conventional form completely and higher concentrations of the inhibitors (100 to 1000 mg/L) was required to inhibit the liposome-entrapped polymyxin B. Co-incubation with inhibitory factors (1000 mg/L) increased conventional (16-fold) and liposomal (4-fold) tobramycin minimum bactericidal concentrations (MBCs), while both polymyxin B formulations were inhibited 64-fold. CONCLUSIONS:Liposome-entrapment reduced antibiotic inhibition up to 100-fold and the CFU of endogenous P. aeruginosa in sputum by 4-fold compared to the conventional antibiotic, suggesting their potential applications in CF lung infections

Clinical and Demographic Factors Associated with COVID-19, Severe COVID-19, and SARS-CoV-2 Infection in Adults: A Secondary Cross-Protocol Analysis of 4 Randomized Clinical Trials

Importance: Current data identifying COVID-19 risk factors lack standardized outcomes and insufficiently control for confounders. Objective: To identify risk factors associated with COVID-19, severe COVID-19, and SARS-CoV-2 infection. Design, Setting, and Participants: This secondary cross-protocol analysis included 4 multicenter, international, randomized, blinded, placebo-controlled, COVID-19 vaccine efficacy trials with harmonized protocols established by the COVID-19 Prevention Network. Individual-level data from participants randomized to receive placebo within each trial were combined and analyzed. Enrollment began July 2020 and the last data cutoff was in July 2021. Participants included adults in stable health, at risk for SARS-CoV-2, and assigned to the placebo group within each vaccine trial. Data were analyzed from April 2022 to February 2023. Exposures: Comorbid conditions, demographic factors, and SARS-CoV-2 exposure risk at the time of enrollment. Main Outcomes and Measures: Coprimary outcomes were COVID-19 and severe COVID-19. Multivariate Cox proportional regression models estimated adjusted hazard ratios (aHRs) and 95% CIs for baseline covariates, accounting for trial, region, and calendar time. Secondary outcomes included severe COVID-19 among people with COVID-19, subclinical SARS-CoV-2 infection, and SARS-CoV-2 infection. Results: A total of 57692 participants (median [range] age, 51 [18-95] years; 11720 participants [20.3%] aged ≥65 years; 31058 participants [53.8%] assigned male at birth) were included. The analysis population included 3270 American Indian or Alaska Native participants (5.7%), 7849 Black or African American participants (13.6%), 17678 Hispanic or Latino participants (30.6%), and 40745 White participants (70.6%). Annualized incidence was 13.9% (95% CI, 13.3%-14.4%) for COVID-19 and 2.0% (95% CI, 1.8%-2.2%) for severe COVID-19. Factors associated with increased rates of COVID-19 included workplace exposure (high vs low: aHR, 1.35 [95% CI, 1.16-1.58]; medium vs low: aHR, 1.41 [95% CI, 1.21-1.65]; P <.001) and living condition risk (very high vs low risk: aHR, 1.41 [95% CI, 1.21-1.66]; medium vs low risk: aHR, 1.19 [95% CI, 1.08-1.32]; P <.001). Factors associated with decreased rates of COVID-19 included previous SARS-CoV-2 infection (aHR, 0.13 [95% CI, 0.09-0.19]; P <.001), age 65 years or older (aHR vs age <65 years, 0.57 [95% CI, 0.50-0.64]; P <.001) and Black or African American race (aHR vs White race, 0.78 [95% CI, 0.67-0.91]; P =.002). Factors associated with increased rates of severe COVID-19 included race (American Indian or Alaska Native vs White: aHR, 2.61 [95% CI, 1.85-3.69]; multiracial vs White: aHR, 2.19 [95% CI, 1.50-3.20]; P <.001), diabetes (aHR, 1.54 [95% CI, 1.14-2.08]; P =.005) and at least 2 comorbidities (aHR vs none, 1.39 [95% CI, 1.09-1.76]; P =.008). In analyses restricted to participants who contracted COVID-19, increased severe COVID-19 rates were associated with age 65 years or older (aHR vs <65 years, 1.75 [95% CI, 1.32-2.31]; P <.001), race (American Indian or Alaska Native vs White: aHR, 1.98 [95% CI, 1.38-2.83]; Black or African American vs White: aHR, 1.49 [95% CI, 1.03-2.14]; multiracial: aHR, 1.81 [95% CI, 1.21-2.69]; overall P =.001), body mass index (aHR per 1-unit increase, 1.03 [95% CI, 1.01-1.04]; P =.001), and diabetes (aHR, 1.85 [95% CI, 1.37-2.49]; P <.001). Previous SARS-CoV-2 infection was associated with decreased severe COVID-19 rates (aHR, 0.04 [95% CI, 0.01-0.14]; P <.001). Conclusions and Relevance: In this secondary cross-protocol analysis of 4 randomized clinical trials, exposure and demographic factors had the strongest associations with outcomes; results could inform mitigation strategies for SARS-CoV-2 and viruses with comparable epidemiological characteristics

Neutralization titer biomarker for antibody-mediated prevention of HIV-1 acquisition

The Antibody Mediated Prevention trials showed that the broadly neutralizing antibody (bnAb) VRC01 prevented acquisition of human immunodeficiency virus-1 (HIV-1) sensitive to VRC01. Using AMP trial data, here we show that the predicted serum neutralization 80% inhibitory dilution titer (PT80) biomarker—which quantifies the neutralization potency of antibodies in an individual’s serum against an HIV-1 isolate—can be used to predict HIV-1 prevention efficacy. Similar to the results of nonhuman primate studies, an average PT80 of 200 (meaning a bnAb concentration 200-fold higher than that required to reduce infection by 80% in vitro) against a population of probable exposing viruses was estimated to be required for 90% prevention efficacy against acquisition of these viruses. Based on this result, we suggest that the goal of sustained PT80 &lt;200 against 90% of circulating viruses can be achieved by promising bnAb regimens engineered for long half-lives. We propose the PT80 biomarker as a surrogate endpoint for evaluatinon of bnAb regimens, and as a tool for benchmarking candidate bnAb-inducing vaccines

Illegal Immigration, Deportation Policy, and the Optimal Timing of Return

Countries with strict immigration policies often resort to deportation measures to reduce their stocks of illegal immigrants. Many of their undocumented foreign workers, however, are not deported but rather choose to return home voluntarily. This paper studies the optimizing behavior of undocumented immigrants who continuously face the risk of deportation, modeled by a stochastic process, and must decide how long to remain in the host country. It is found that the presence of uncertainty with respect to the length of stay abroad unambiguously reduces the desired migration duration and may trigger a voluntary return when a permanent stay would otherwise be optimal. Voluntary return is motivated by both economic and psychological factors. Calibration of the model to match the evidence on undocumented Thai migrants in Japan suggests that the psychological impact of being abroad as an illegal alien may be equivalent to as large as a 68% cut in the consumption rate at the point of return