Is venous thrombembolism during pregnancy an indication for routine assay of antithrombin activity and antithrombin supplementation?

Summary During pregnancy the concentrations of many coagulation factors are increased what leads to a „physiological” hypercoagulability status and constitutes a natural protection against delivery hemorrhage. These changes may be conducive to venous thrombembolism. Antithrombin is one of the endogenous clotting inhibitors. As a serine protease, it inactivates thrombin and the efficiency of this reaction is intensified by heparin. Acquired antithrombin deficiency is caused by disseminated intravascular coagulation syndrome, deep vein thrombosis, neoplasms, nephritic syndrome, renal failure, liver diseases, long-term estrogen treatment, dialysis or extracorporeal circulation. There are also cases of inherited antithrombin deficiency which leads to thrombophilia. The following study presents a course of pregnancy and postpartum of a woman with deep vein thrombosis and acquired antithrombin deficiency, as well as the applied treatment. The legitimacy of routine assay of antithrombin activity and antithrombin supplementation in pregnant women with thrombosis was considered. This procedure may be helpful when dealing with obese pregnant patients as it is difficulty to identify and establish a therapeutic dose of heparin in their cases. Therapy guidelines for pregnant patients with thrombosis and acquired antithrombin deficiency have not been established yet

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

Anaemia in Acute HIV-1 Subtype C Infection

BACKGROUND: The high prevalence of anaemia and the increased morbidity and mortality associated with anaemia during AIDS has been well described yet there has been little information about anaemia and changes in haemoglobin levels during acute and early HIV-1 infection. METHODS: HIV-negative women (n = 245) were enrolled into an observational cohort as part of the Centre for the AIDS Programme of Research in South Africa (CAPRISA) Acute Infection Study. Acute infection was diagnosed following a positive HIV RNA PCR in the absence of antibodies, or detection of HIV-1 antibodies within 3 months of a previously negative antibody test. Haemotologic parameters were assessed before infection and at regular intervals in the first twelve months of HIV infection. RESULTS: Fifty-seven participants with acute HIV infection were identified at a median of 14.5 days post-infection (range 10-81) and were enrolled in the CAPRISA Acute Infection cohort at a median of 41 days post-infection (range 15-104). Mean haemoglobin prior to HIV-1 infection was 12.7 g/dL, with a mean decline of 0.46 g/dL following infection. The prevalence of anaemia increased from 25.0% prior to HIV-1 infection to 52.6% at 3 months post-infection, 61.1% at 6 months post-infection, and 51.4% at 12 months post-infection. CONCLUSIONS: Haematologic derangements and anaemia with a trend towards iron deficiency are common with acute HIV-1 subtype C infection in this small cohort. The negative impact of anaemia concurrent with established HIV infection upon morbidity and mortality has been well documented but the prognostic potential and long-term effects of anaemia during acute HIV-1 infection remain unknown

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

Recommendations for the follow-up of study participants with breakthrough HIV infections during HIV/AIDS biomedical prevention studies.

CAPRISA_2013.Objective: To facilitate collection of cumulative data on longitudinal HIV disease outcomes during HIV prevention studies by developing recommendations for follow-up of the relatively few study participants with breakthrough infections. Design: We formed a working group to compare and contrast the various approaches taken in recent HIV prevention trials, to summarize the advantages and disadvantages associated with each, and to explore the feasibility of developing protocols for the long-term follow-up of seroconverters. Methods: We reviewed study designs, objectives, and assessments in 15 interventional studies that followed HIV seroconverters. Protocol team members joined discussions of the various approaches and developed recommendations. Results: Most HIV prevention clinical trials share a core set of objectives, including the description/comparison of virological, immunological, and clinical course of HIV, and sometimes a comparison of preseroconversion and postseroconversion behavior. Long-term follow-up of seroconverters can be conducted in separate studies if the transition from parent protocol is effectively managed. Conclusion: We recommend the development of harmonized seroconverter protocols. Although specific research questions in the postseroconversion period may differ depending on prevention modality, harmonizing key evaluations would create an opportunity to ask overarching questions that inform the prevention field with respect to design and implementation of future combination prevention studies. Follow-up immediately postseroconversion should be conducted in the parent protocol before roll over into a follow-up protocol. Development of specimen repositories with ample volumes for future assays, standardized definitions of infection, diagnosis and seroconversion dates, and harmonization of study objectives and sample collections at key time points are important

Changes in SARS-CoV-2 viral load and mortality during the initial wave of the pandemic in New York City

Funding: This work was partially supported by the National Center for Advancing Translational Sciences of the National Institutes of Health (UL1 TR0023484 to Julianne Imperato-McGinley) and the National Institute of Allergy and Infectious Diseases (UM1 AI069470 to M.E.S).Public health interventions such as social distancing and mask wearing decrease the incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but it is unclear whether they decrease the viral load of infected patients and whether changes in viral load impact mortality from coronavirus disease 2019 (COVID-19). We evaluated 6923 patients with COVID-19 at six New York City hospitals from March 15-May 14, 2020, corresponding with the implementation of public health interventions in March. We assessed changes in cycle threshold (CT) values from reverse transcription-polymerase chain reaction tests and in-hospital mortality and modeled the impact of viral load on mortality. Mean CT values increased between March and May, with the proportion of patients with high viral load decreasing from 47.7% to 7.8%. In-hospital mortality increased from 14.9% in March to 28.4% in early April, and then decreased to 8.7% by May. Patients with high viral loads had increased mortality compared to those with low viral loads (adjusted odds ratio 2.34). If viral load had not declined, an estimated 69 additional deaths would have occurred (5.8% higher mortality). SARS-CoV-2 viral load steadily declined among hospitalized patients in the setting of public health interventions, and this correlated with decreases in mortality.Peer reviewe

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 serostatus disclosure is not associated with safer sexual behavior among HIV-positive men who have sex with men (MSM) and their partners at risk for infection in Bangkok, Thailand

Background: The relationship between HIV serostatus disclosure and sexual risk behavior is inconsistent across studies. As men who have sex with men (MSM) are emerging as the key affected population in Bangkok, Thailand with reported HIV prevalence of 30%, we assessed whether HIV disclosure is associated with protected sex in this population. Methods: A risk behavior questionnaire was administered using Audio Computer-Assisted Self-Interviewing (ACASI) to determine whether HIV serostatus disclosure was associated with protected sex in 200 HIV-positive MSM in Bangkok. HIV serostatus disclosure to the most recent sexual partner prior to or at the time of the sexual encounter was assessed. Protected sex was defined as insertive or receptive anal intercourse with a condom at the most recent sexual encounter. Results: The mean age was 30.2 years, CD4 was 353 cells/mm³, and one-third was on antiretroviral therapy. At the most recent sexual encounter, HIV serostatus disclosure rate was low (26%); 60.5% of subjects had not discussed their serostatus at all, while 5.5% had not revealed their true serostatus. Seventeen percent reported unprotected anal intercourse and about half had sex with their primary partners. The serostatus of the most recent sexual partner was HIV-positive in 19.2%, HIV-negative in 26.4%, and unknown in 54.4% of subjects. There was no association between disclosure and protected sex, with 41 of 48 (85.4%) disclosers and 104 of 126 (82.5%) of non-disclosers reported protected sex (p = .65). Subjects with HIV-positive partners were less likely to report protected sex overall (20 of 33, 60.6%) compared to those with HIV negative (82 of 96, 85.4%) or unknown (41 of 45, 91.1%) partners (p = .001). Age (27-32 years vs. ≤26 years, p = .008), primary partner status (p < .001), and HIV-positive serostatus of sexual partner (p < .001) were significantly associated with disclosure in the multivariate analyses. Conclusion: Rates of HIV disclosure to sexual partners by HIV-positive MSM in Bangkok are low. Despite low rates of HIV serostatus disclosure, most HIV-positive MSM reported protected sex with their partners at risk for infection. Future studies should focus on understanding barriers to disclosure and factors driving risk behavior amongst MSM in Thailand

Antibody Evasion by SARS-CoV-2 Omicron Subvariants BA2121, BA4 and BA5

SARS-CoV-2 Omicron subvariants BA.2.12.1 and BA.4/5 have surged notably to become dominant in the United States and South Africa, respectively1,2. These new subvariants carrying further mutations in their spike proteins raise concerns that they may further evade neutralizing antibodies, thereby further compromising the efficacy of COVID-19 vaccines and therapeutic monoclonals. We now report findings from a systematic antigenic analysis of these surging Omicron subvariants. BA.2.12.1 is only modestly (1.8-fold) more resistant to sera from vaccinated and boosted individuals than BA.2. However, BA.4/5 is substantially (4.2-fold) more resistant and thus more likely to lead to vaccine breakthrough infections. Mutation at spike residue L452 found in both BA.2.12.1 and BA.4/5 facilitates escape from some antibodies directed to the so-called class 2 and 3 regions of the receptor-binding domain3. The F486V mutation found in BA.4/5 facilitates escape from certain class 1 and 2 antibodies but compromises the spike affinity for the viral receptor. The R493Q reversion mutation, however, restores receptor affinity and consequently the fitness of BA.4/5. Among therapeutic antibodies authorized for clinical use, only bebtelovimab retains full potency against both BA.2.12.1 and BA.4/5. The Omicron lineage of SARS-CoV-2 continues to evolve, successively yielding subvariants that are not only more transmissible but also more evasive to antibodies