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The article presents a case study of a 20-year-old man with a history of electronic-cigarette use, also known as vaping, was evaluated in the pulmonary clinic of U.S. hospital. Because of progressive dyspnea and abnormal findings on chest imaging the patient firstly treated with empirical antibiotic but after knowing about thrombotic antiphospholipid antibody syndrome of patients he was treated with systemic anticoagulation along with prednisone, two doses of rituximab.

Background: An effective therapeutic vaccine that could augment immune control of HIV-1 replication may abrogate or delay the need for antiretroviral therapy. AIDS Clinical Trials Group (ACTG) A5187 was a phase I/II, randomized, placebocontrolled, double-blinded trial to evaluate the safety and immunogenicity of an HIV-1 DNA vaccine (VRC-HVDNA 009-00- VP) in subjects treated with antiretroviral therapy during acute/early HIV-1 infection. (clinicaltrials.gov NCT00125099) Methods: Twenty healthy HIV-1 infected subjects who were treated with antiretroviral therapy during acute/early HIV-1 infection and had HIV-1 RNA<50 copies/mL were randomized to receive either vaccine or placebo. The objectives of this study were to evaluate the safety and immunogenicity of the vaccine. Following vaccination, subjects interrupted antiretroviral treatment, and set-point HIV-1 viral loads and CD4 T cell counts were determined 17-23 weeks after treatment discontinuation. Results: Twenty subjects received all scheduled vaccinations and discontinued antiretroviral therapy at week 30. No subject met a primary safety endpoint. No evidence of differences in immunogenicity were detected in subjects receiving vaccine versus placebo. There were also no significant differences in set-point HIV-1 viral loads or CD4 T cell counts following treatment discontinuation. Median set-point HIV-1 viral loads after treatment discontinuation in vaccine and placebo recipients were 3.5 and 3.7 log10 HIV-1 RNA copies/mL, respectively. Conclusions: The HIV-1 DNA vaccine (VRC-HIVDNA 009-00-VP) was safe but poorly immunogenic in subjects treated with antiretroviral therapy during acute/early HIV-1 infection. Viral set-points were similar between vaccine and placebo recipients following treatment interruption. However, median viral load set-points in both groups were lower than in historical controls, suggesting a possible role for antiretroviral therapy in persons with acute or early HIV-1 infection and supporting the safety of discontinuing treatment in this group. Trial Registration: Clinicaltrials.gov NCT00125099. [ABSTRACT FROM AUTHOR]

The article discusses the case of a 47 year old man with acute HIV infection. A description of his course of illness is presented. The differential diagnosis which included a bacterial infection that spread to the meninges is discussed. A discussion which examines the involvement of atypical bacterial, fungal, or parasitic infection is presented. Viral infections that cause fever and rash as seen in this man are also examined.

Emerging evidence suggests that early events in human immunodeficiency virus type 1 (HIV-1) infection may play a critical role in determining disease progression. Although there is limited evidence on which to base medical decisions, the diagnosis and treatment of acute HIV-1 infection may have virologic, immunologic, and clinical benefits. In addition, rapid diagnosis of infection may prevent unknowing transmission of HIV-1 during a period of high-level viremia. We review the basic principles of primary HIV-1 infection, clinical and diagnostic markers of acute seroconversion, approaches to management, and new therapeutic strategies. [ABSTRACT FROM AUTHOR]

The development and implementation of highly active antiretroviral therapy (HAART) for the treatment of the human immunodeficiency virus has revolutionised the care of patients with this disease. Despite the positive impact that antiretroviral therapy has had on the lives of individuals with HIV infection, the adverse effects, potential long-term toxicities, complexity of regimens, development of drug resistance and cost have made decisions about when to initiate HAART difficult. The benefits and risks of antiretroviral therapy vary considerably among patients at different stages of disease, mainly as a result of the irreversible destruction of the immune system that occurs as HIV infection progresses. In acute HIV infection, the primary aim of treatment is preservation and reconstitution of HIV-specific immune function. In symptomatic or late-stage disease, the goal is control of viral replication with resulting improvement in non-HIV-specific immunity, which leads to decreased morbidity and increased survival. The most controversial decision involves when to start therapy in persons with asymptomatic chronic HIV, where the benefits are less well established and may be outweighed by the drawbacks, depending on the individual patient. In all patients, the advantages and disadvantages must be considered carefully, and the readiness and ability of the individual to adhere to a complex multidrug regimen needs to be assessed before the initiation of therapy. [ABSTRACT FROM AUTHOR]

Presents a study in which treatment interruptions were administered to eight HIV-positive subjects with treated acute infection, with the plan to restart therapy if the viral load exceeded a certain level. Viral load below 5,000 RNA copies per milliliter which was acheived by all subjects; Observation of increased virus-specific cytotoxic T lymphocytes and maintained T-helper-cell responses; Indication that functional immune responses can be augmented in a chronic viral infection; Rationale for immunotherapy in HIV-1 infection.

Presents research which studied HIV-1-specific CD4+ T cell proliferative responses in various types of AIDS patients. Importance of virus-specific CD4+ T helper lymphocytes; Classes of patients studied according to severity of infection and use of antiviral therapy; Role of HIV-1-specific helper cells.

The article presents insights on acute human immunodeficiency virus (HIV)-1 infection. The infection is characterized by a flu or mononucleosis-like syndrome, high-level viremia, and a transient decrease in CD4+ T cells in the blood and gut within days to weeks after infection. They provide an overview of the Short Pulse Anti-Retroviral Therapy at Seroconversion (SPARTAC) controlled trial for acute HIV-1 infection.

The author reflects on the reduction of blood culture contamination. It tackles the methods for the reduction of contamination rates which include cleaning the top of the blood culture bottle, avoiding arterial punctures and using trained phlebotomists and blood culture collection kits. It also discusses a trial that assesses the effectiveness of routine use of sterile gloves during peripheral venipuncture to reduce blood culture contamination.

In light of a recent report of 3 false-positive results of Epstein-Barr virus heterophile tests caused by HIV infection, we sought to assess the frequency of this occurrence. One hundred thirty-two positive heterophile antibody-tested serum samples were obtained from 2 tertiary care facilities in Boston to assess for HIV, and all tested negative for HIV plasma RNA. This study shows that false-positive results of heterophile tests are not frequently associated with primary HIV infection. [ABSTRACT FROM AUTHOR]

The author presents information on the recognition of novel infectious diseases related to the Borrelia miyamotoi, bacteria. He informs that B. miyamotoi infection was detected in 46 Russian patients by using species-specific polymerase chain reaction (PCR). He further informs that the full spectrum of illness needs to be defined in case of infection from this bacterium.

The author comments on the study "Prevention of HIV-1 infection with early antiretroviral therapy," by M. S. Cohen, Y. Q. Chen, M. McCauley, et alii, in the August 11, 2011 issue of the "New England Journal of Medicine." The study evaluated the effects of antiretroviral combination therapy on heterosexual transmission of human immunodeficiency virus type 1 (HIV-1). The author highlights the positive results of the study that proves that the treatment can be used for HIV-1 prevention strategy.

Cites a study published in the October 2000 issue of 'Nature Medicine,' concerning apparent successful immune containment of an AIDS-like virus after drug therapy and therapeutic immunization administered early after initial infection in an animal model. Benefits and drawbacks of highly active antiviral therapy; Possibility of boosting cellular immunity by therapeutic immunization.

Background. Individuals infected with human immunodeficiency virus (HIV) have decreased high-density lipoprotein (HDL)-cholesterol and increased cardiovascular disease (CVD). Reverse cholesterol transport from macrophages may be inhibited by HIV and contribute to increased CVD. Human studies have not investigated longitudinal effects of HIV and antiretroviral therapy (ART) on cholesterol efflux.Methods. Subjects with acute HIV infection were randomized to ART or not. Cholesterol efflux capacity was determined ex vivo after exposure of murine macrophages to apolipoprotein B-depleted patient sera obtained at baseline and after 12 weeks.Results. After 12 weeks, HIV RNA decreased most in subjects randomized to ART. Available data on cholesterol demonstrated that efflux capacity from Abca1+/+ macrophages was increased most by sera obtained from ART-treated subjects (20.5% ± 5.0% to 24.3 % ± 6.9%, baseline to 12 weeks, P = .007; ART group [n = 6] vs 18.0 % ± 3.9% to 19.1 % ± 2.9%, baseline to 12 weeks, P = .30; untreated group [n = 6] [P = .04 ART vs untreated group]). Change in HIV RNA was negatively associated with change in Abca1+/+ macrophage cholesterol efflux (r = − 0.62, P = .03), and this finding remained significant (P = .03) after controlling for changes in HDL-cholesterol, CD4+ cells, and markers of monocyte or macrophage activation.Conclusions. In subjects acutely infected with HIV, ATP-binding cassette transporter A1-mediated cholesterol efflux was stimulated to a greater degree over time by apolipoprotein B-depleted serum from subjects randomized to ART. The improvement in cholesterol efflux capacity is independently related to reduction in viral load. [ABSTRACT FROM PUBLISHER]

Abstract: The goal of this article is to suggest that mathematical models describing biological processes taking place within a patient over time can be used to design adaptive treatment strategies. We demonstrate using the key example of treatment strategies for human immunodeficiency virus type-1 (HIV) infection. Although there has been considerable progress in management of HIV infection using highly active antiretroviral therapies, continuous treatment with these agents involves significant cost and burden, toxicities, development of drug resistance, and problems with adherence; these latter complications are of particular concern in substance-abusing individuals. This has inspired interest in structured or supervised treatment interruption (STI) strategies, which involve cycles of treatment withdrawal and re-initiation. We argue that the most promising STI strategies are adaptive treatment strategies. We then describe how biological mechanisms governing the interaction over time between HIV and a patient''s immune system may be represented by mathematical models and how control methods applied to these models can be used to design adaptive STI strategies seeking to maintain long-term suppression of the virus. We advocate that, when such mathematical representations of processes underlying a disease or disorder are available, they can be an important tool for suggesting adaptive treatment strategies for clinical study. [Copyright &y& Elsevier]

A letter to the editor is presented about acute infection with HIV-1 and its association with a mononucleosis-like illness in patients.

There are emerging reports of false-positive HIV nucleic acid testing (NAT) in patients who have received chimeric antigen receptor (CAR) T-cell therapies. We present a case of a 66-year-old-woman with primary-refractory stage IIIA double-hit high-grade B-cell lymphoma, in whom we detected false-positive HIV-1 NAT results after receipt of a third-generation self-inactivating investigational lentivirus-based CAR T-cell therapy. We reviewed the current state of the science on HIV-1 NAT and found that all reported false-positive cases have occurred in the setting of lentivirus-based CAR T-cell therapy and testing with FDA-approved platforms targeting the 5'LTR genomic region. Herein, we offer recommendations for HIV diagnostic testing in patients undergoing this mode of therapy. Clinicians managing this patient population should be aware of cross-reactivity between these therapeutic agents and commonly used HIV-1 NAT assays. [ABSTRACT FROM AUTHOR]

In this randomized controlled trial, active screening was superior to passive screening for discontinuation of contact precautions for methicillin-resistant Staphylococcus aureus, and a single negative nasal swab processed by polymerase chain reaction had a high negative predictive value compared to 3 nasal cultures.Background. There have been no randomized controlled trials comparing active and passive screening for documenting clearance of colonization with methicillin-resistant Staphylococcus aureus (MRSA). We compared the efficacy of active and passive screening using both culture and commercial polymerase chain reaction (PCR) for documentation of MRSA clearance and discontinuation of MRSA contact precautions (CPs).Methods. Inpatients with a history of MRSA infection or colonization enrolled between December 2010 and September 2011 were randomized to either passive (nonintervention arm; n = 202; observation with local standard of care) or active screening (intervention arm; n = 405; study staff screened using culture and commercial PCR). The primary outcome was discontinuation of CPs by trial arm based on 3 negative cultures. In the intervention arm, sensitivity, specificity, and positive and negative predictive values of the first PCR were compared to cultures.Results. CPs were discontinued significantly more often (rate ratio [RR], 4.1; 95% confidence interval [CI], 2.3%–7.1%) in the intervention arm, including in an intent-to-screen analysis (RR, 2.6; 95% CI, 1.5%–4.7%). The first PCR, compared to 3 cultures, detected MRSA with a sensitivity of 93.9% (95% CI, 85.4%–97.6%), a specificity of 92.0% (95% CI, 85.9%–95.6%), a positive predictive value of 86.1% (95% CI, 75.9%–93.1%), and a negative predictive value of 96.6% (95% CI, 91.6%–99.1%).Conclusions. Compared to passive screening using culture methods, active screening resulted in discontinuation of MRSA CPs at a significantly higher frequency. Active screening with a single PCR would significantly increase the completion of the screening process.Clinical Trials Registration. NCT01234831. [ABSTRACT FROM PUBLISHER]

The article describes the case of a 43-year-old pregnant woman who was admitted to the labor and delivery service of a hospital due to vaginal bleeding. Her medical history included obesity and migraine headaches. During cesarean delivery, the patient experienced suddent onset of bradycardia, chest pain, loss of consciousness and apnea. She was diagnosed with amniotic-fluid embolism. Treatment options for her condition are mechanical circulatory support and extracorporeal membrane oxygenation.

The article describes the case of a 55-year-old man who experienced alcohol withdrawal delirium and multifactorial delirium. The patient was admitted to the intensive care unit (ICU) at the Massachusetts General Hospital because of seizures and agitation. He was found to be confused and afebrile after he stopped drinking alcohol. Signs and symptoms of alcohol withdrawal delirium include hallucinations, hypertension, tachycardia, fever and diaphoresis.

The article describes the case of a male patient who presented to a hospital with abdominal pain. Computed tomography angiography (CTA) revealed dilated distal abdominal aorta. The patient underwent a right axillobifemoral bypass operation and was given several medications including vancomycin and ceftriaxone. The patient returned to the hospital after one month due to chest and back pain. CTA revealed an enlargement of the aneurysm of the descending thoracic aorta.

The article describes the case of a 21-year-old man admitted to a hospital due to arthralgias, dyspnea, and pulmonary infiltrates and was readmitted after a month due to persistent fatigue, myalgias, knee pain, and night sweats. The man was diagnosed to have a protracted illness which started 14 months before his second admission to the hospital. The patient has interstitial lung disease but it is questioned whether it is an idiopathic form or is associated with a specific disease process.

The article discusses the clinical case of a 16-year-old girl who was admitted due to trauma and extensive burns sustained in a motor-vehicle accident. The physical and laboratory findings on the patient are described. The therapeutic and rehabilitation approaches administered to the patient are described, including the psychiatric management given to the patient. Clinical information on traumatic brain injury is also provided.

The article discusses the case of a male patient diagnosed with profound hypothyroidism. The patient presented to the hospital with weakness, anorexia, malaise, history of falling and diffuse pain. The patient has a history of renal transplantation due to renal failure. Following the diagnosis of profound hypothyroidism, the patient was managed with intravenous levothyroxine and continuous venovenous hemofiltration. The patient developed infections and eventually died.

The article describes the case of a 27-year-old pregnant woman who had experienced spontaneous rupture of a gravid uterus on the left posterolateral wall with hematometra. The patient experienced abdominal pain during labor with cessation of contractions and vaginal bleeding before she was admitted to a hospital in Ethiopia. The possible causes of this condition are chorioamnionitis, placental abruption and uterine rupture.

The article describes the case of a 34-year-old woman with glucose homeostasis and hypoglycemia. The patient experienced symptoms such as episodes of altered mental status and amnesia. She underwent the differential diagnosis of altered mental status and an electrocardiogram. Causes of hypoglycemia include the treatment of diabetes.

The article describes the case of a 35-year-old man presented with dyspnea, anemia, and renal failure. The patient was in respiratory distress according to the examination conducted. His cytologic examination revealed evidence of acute inflammation and pulmonary macrophages, with no malignant cells.

The article describes the case of an 18-year-old man presented with blurred vision, dysarthria and ataxia, which had reportedly progressed to coma. The patient had an abrupt onset of weakness, shaking and buckling of his legs, and clumsiness of his right hand the evening before his admission. Details of the results of his physical and laboratory examinations are discussed. Information on the initial management of the patient is also provided.

Background: Enzalutamide (formerly called MDV3100) targets multiple steps in the androgen-receptor–signaling pathway, the major driver of prostate-cancer growth. We aimed to evaluate whether enzalutamide prolongs survival in men with castration-resistant prostate cancer after chemotherapy. Methods: In our phase 3, double-blind, placebo-controlled trial, we stratified 1199 men with castration-resistant prostate cancer after chemotherapy according to the Eastern Cooperative Oncology Group performance-status score and pain intensity. We randomly assigned them, in a 2:1 ratio, to receive oral enzalutamide at a dose of 160 mg per day (800 patients) or placebo (399 patients). The primary end point was overall survival. Results: The study was stopped after a planned interim analysis at the time of 520 deaths. The median overall survival was 18.4 months (95% confidence interval [CI], 17.3 to not yet reached) in the enzalutamide group versus 13.6 months (95% CI, 11.3 to 15.8) in the placebo group (hazard ratio for death in the enzalutamide group, 0.63; 95% CI, 0.53 to 0.75; P<0.001). The superiority of enzalutamide over placebo was shown with respect to all secondary end points: the proportion of patients with a reduction in the prostate-specific antigen (PSA) level by 50% or more (54% vs. 2%, P<0.001), the soft-tissue response rate (29% vs. 4%, P<0.001), the quality-of-life response rate (43% vs. 18%, P<0.001), the time to PSA progression (8.3 vs. 3.0 months; hazard ratio, 0.25; P<0.001), radiographic progression-free survival (8.3 vs. 2.9 months; hazard ratio, 0.40; P<0.001), and the time to the first skeletal-related event (16.7 vs. 13.3 months; hazard ratio, 0.69; P<0.001). Rates of fatigue, diarrhea, and hot flashes were higher in the enzalutamide group. Seizures were reported in five patients (0.6%) receiving enzalutamide. Conclusions: Enzalutamide significantly prolonged the survival of men with metastatic castration-resistant prostate cancer after chemotherapy. (Funded by Medivation and Astellas Pharma Global Development; AFFIRM ClinicalTrials.gov number, NCT00974311.) [ABSTRACT FROM PUBLISHER]

The article discusses the medical case of a 49-year-old man presented with fever, pain and cranial nerve deficits after squamous-cell cancer of the oral cavity treatment. The patient's medical history is detailed. Results of pathological examination on the patient are discussed as well as the differential diagnosis centered on an infectious process and recurrent cancer. Management of squamous-cell carcinoma of the head and neck and the risk of r5ecurrence are discussed.

The article describes the case of a 30-year-old woman presented with shock and abdominal-wall necrosis after a cesarean section. The patient had undergone cesarean section at 36.4 weeks gestation due to suspected chorioamnionitis, fetal tachycardia and a prolonged deceleration on a fetal heart-rate tracing during labor augmented by oxytocin. Her medications on admission included prenatal vitamins, iron and acetaminophen. Details of the results of her laboratory tests are discussed.

The article describes the case of a 60-year-old woman who complained of painful muscle spasms, weakness and hyperreflexia. Information on her medical history is provided, as well as the results of her laboratory tests. Degenerative changes of both the cervical and lumbar spine were detective via magnetic resonance imaging. Differential diagnosis include limbic encephalitis and herpes encephalitis. She was diagnosed with stiff person syndrome and anti-amphiphysin antibodies.

The article presents a case study of an old woman diagnosed with back pain and fever. The magnetic resonance imaging (MRI) examination of the patient shows inflammatory changes in her adjacent epidural space and paraspinal soft tissues. It notes that she did not have obvious cortical destruction that usually has bacterial osteomyelitis.

The article describes the case of a 15-year-old boy who was admitted to the hospital because of recurrent abdominal pain and diarrhea. The boy also developed episodes of midline low back pain, which were worse in the morning and improved with activity and flexion. Details of the results of his examinations are discussed. He was diagnosed with iron-deficiency anemia, thalassemia minor, obesity, borderline hypertension, mild asthma, and eczema. Irritable bowel syndrome was also considered.

Best practice for the clinical management of acute human immunodeficiency virus (HIV) infection remains unknown. Although some data suggest possible immunologic, virologic, or clinical benefit of early treatment, other studies show no difference in these outcomes over time, after early treatment is discontinued. The literature on acute HIV infection is predominantly small nonrandomized studies, which further limits interpretation. As a result, the physician is left to grapple with these uncertainties while making clinical decisions for patients with acute HIV infection. Here we review the literature, focusing on the potential advantages and disadvantages of treating acute HIV infection outlined in treatment guidelines, and summarize the presentations on clinical management of acute HIV infection from the 2009 Acute HIV Infection Meeting in Boston, Massachusetts. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 29-year-old woman who was admitted to a hospital for increasing abdominal pain and fever and was later diagnosed to be suffering from Epstein-Barr viral infection or infectious mononucleosis. The patient has cerebral palsy and spastic quadriplegia. The day before admission, she observed foul-smelling urine and pain in the left lower quadrant and the left flank.

Background. Examination of multiple stool specimens per patient to rule out parasitic infection continues to be recommended in the literature. Attractive alternatives have been proposed, such as examination of a single specimen, but data to support their use have been inconclusive. Methods. We reviewed the results of comprehensive stool ova and parasite examinations performed during a 1-year period to determine the incremental value of examining >1 specimen. Next, we implemented rejection criteria, allowing analysis of only a single specimen in most cases, and studied the impact of the change by reviewing data from a subsequent year. Results. Prior to implementation of rejection criteria, 91% of parasites were detected in the first specimen submitted, although many clinical evaluations (72%) involved the submission of only 1 stool specimen. When at least 3 specimens were submitted, the sensitivity of examining the first in the series was 72%. Even the latter sensitivity provides negative predictive values of ∼98%, ∼97%, ∼95%, or ∼93% when the prevalence of parasites among those tested is 5%, 10%, 15%, or 20%, respectively. Examination of additional specimens after examination of the first specimen that yielded a positive finding revealed previously undetected parasites in only 10% of cases. After the application of rejection criteria, the parasite detection rate did not change significantly. Conclusions. Comprehensive examination of a single stool specimen is sufficient for most patients, when the prevalence of infection among the tested population is up to 20%. Rational use of the stool ova and parasite examination relies on communication between clinician and laboratory, and retention of deferred specimens in case examination of additional specimens is clinically warranted. [ABSTRACT FROM AUTHOR]

Background. The diagnosis of human immunodeficiency virus type 1 (HIV-1) infection by standard tests relies on the formation of HIV- 1-specific antibodies. Early treatment of acute HIV- 1 infection may have unique immunologic effects on host cellular and humoral responses. Rare cases of HIV- 1 seroreversion have been reported for patients with advanced or rapidly progressive disease. Here, we report seroreversion that occurred in subjects with acute HIV- 1 infection who initiated early antiretroviral therapy. Methods. A total of 150 patients with symptomatic acute or early onset HIV- 1 infection that was treated with antiretroviral therapy were observed prospectively by means of monthly clinical and laboratory evaluation, which included serial HIV enzyme-linked immunosorbent assay and Western blots, until a fully evolved HIV-1 antibody response was documented. Results. Three patients who initiated antiretroviral therapy a mean interval of 8 days (range, 1-16 days) after presentation and were observed for a mean duration of 50.2 months (range, 40.2-55.7 months) did not develop a fully evolved HIV- 1 antibody response or demonstrated complete or partial HIV- 1 seroreversion, despite maintenance of cytomegalovirus-specific humoral responses. Virologic suppression and seroreversion (complete or partial) occurred a mean duration of 4.1 months (range, 2.3-5.7 months) and 15.5 months (range, 6.7-26.3 months), respectively, after the initiation of therapy. All patients maintained complete virologic suppression while receiving therapy and had an undetectable HIV- 1 RNA load at the time of seroreversion. Conclusions. Early antiretroviral therapy associated with durable virologic suppression in acute HIV- 1 infection may abrogate the formation or detection of HIV- 1-specific antibodies. Ongoing antigenic stimulation may be required to maintain HIV- 1-specific humoral responses. Incomplete evolution of the HIV- 1 antibody response and/or presence of seroreversion (although infrequently observed) underscore the potential unique immunologic effect of early antiretroviral therapy in patients with primary HIV- 1 infection. [ABSTRACT FROM AUTHOR]

Reports that the HIV-1 regulatory proteins Tat and Rev are frequently targeted by cytotoxic T lymphocytes derived from HIV-1-infected individuals. CD8+ T cell responses against HIV-1 Tat and Rev peptides; Frequency of recognition of Tat and Rev; Differences among distinct groups of HIV-1-infected individuals.

Of the 50 samples confirmed to be Delta by WGS, 47 of 50 (94%) were correctly identified by the mutational panel; for the remaining 3 WGS-confirmed Delta samples, a variant determination could not be made on the basis of the mutation profile (Supplement). Graph: Clinical Characteristics of Patients With Omicron Infection From 1 December to 30 December 2021, we screened 2399 SARS-CoV-2 NAAT-positive specimens for SGTF. I Background: i The emergence of the SARS-CoV-2 Omicron variant has important clinical and therapeutic implications. [Extracted from the article]

High rates of asymptomatic coronavirus disease 2019 infection suggest benefits to routine testing in congregate care settings. Screening was undertaken in a single nursing facility without a known case of coronavirus disease 2019, demonstrating an 85% prevalence among residents and 37% among staff. Serology was not helpful in identifying infections. [ABSTRACT FROM AUTHOR]

Background Amid the enduring pandemic, there is an urgent need for expanded access to rapid, sensitive, and inexpensive coronavirus disease 2019 (COVID-19) testing worldwide without specialized equipment. We developed a simple test that uses colorimetric reverse transcription loop-mediated isothermal amplification (RT-LAMP) to detect severe acute resrpiratory syndrome coronavirus 2 (SARS-CoV-2) in 40 minutes from sample collection to result. Methods We tested 135 nasopharyngeal specimens from patients evaluated for COVID-19 infection at Massachusetts General Hospital. Specimens were either added directly to RT-LAMP reactions, inactivated by a combined chemical and heat treatment step, or inactivated then purified with a silica particle–based concentration method. Amplification was performed with 2 SARS-CoV-2-specific primer sets and an internal specimen control; the resulting color change was visually interpreted. Results Direct RT-LAMP testing of unprocessed specimens could only reliably detect samples with abundant SARS-CoV-2 (>3 000 000 copies/mL), with sensitivities of 50% (95% CI, 28%–72%) and 59% (95% CI, 43%–73%) in samples collected in universal transport medium and saline, respectively, compared with quantitative polymerase chain reaction (qPCR). Adding an upfront RNase inactivation step markedly improved the limit of detection to at least 25 000 copies/mL, with 87.5% (95% CI, 72%–95%) sensitivity and 100% specificity (95% CI, 87%–100%). Using both inactivation and purification increased the assay sensitivity by 10-fold, achieving a limit of detection comparable to commercial real-time PCR-based diagnostics. Conclusions By incorporating a fast and inexpensive sample preparation step, RT-LAMP accurately detects SARS-CoV-2 with limited equipment for about US$6 per sample, making this a potentially ideal assay to increase testing capacity, especially in resource-limited settings. [ABSTRACT FROM AUTHOR]

The article focuses on the Cytomegalovirus (CMV), an important cause of morbidity and mortality in the immunocompromised host. It mentions that human monocytes infected with CMV do not effectively phagocytose fungal pathogens, a functional deficit which occurs with decreased expression of fungal recognition receptors; and also mentions that CMV modulates both immunosuppressive and immunostimulatory monocyte phenotypes.

Background Anaplasmosis presents with fever, headache, and laboratory abnormalities including leukopenia and thrombocytopenia. Polymerase chain reaction (PCR) is the preferred diagnostic but is overutilized. We determined if routine laboratory tests could exclude anaplasmosis, improving PCR utilization. Methods Anaplasma PCR results from a 3-year period, with associated complete blood count (CBC) and liver function test results, were retrospectively reviewed. PCR rejection criteria, based on white blood cell (WBC) and platelet (PLT) counts, were developed and prospectively applied in a mock stewardship program. If rejection criteria were met, a committee mock-refused PCR unless the patient was clinically unstable or immunocompromised. Results WBC and PLT counts were the most actionable routine tests for excluding anaplasmosis. Retrospective review demonstrated that rejection criteria of WBC ≥11 000 cells/µL or PLT ≥300 000 cells/µL would have led to PCR refusal in 428 of 1685 true-negative cases (25%) and 3 of 66 true-positive cases (5%) involving clinically unstable or immunocompromised patients. In the prospective phase, 155 of 663 PCR requests (23%) met rejection criteria and were reviewed by committee, which endorsed refusal in 110 of 155 cases (71%) and approval in 45 (29%), based on clinical criteria. PCR was negative in all 45 committee-approved cases. Only 1 of 110 mock-refused requests yielded a positive PCR result; this patient was already receiving doxycycline at the time of testing. Conclusions A CBC-based stewardship algorithm would reduce unnecessary Anaplasma PCR testing, without missing active cases. Although the prospectively evaluated screening approach involved medical record review, this was unnecessary to prevent errors and could be replaced by a rejection comment specifying clinical situations that might warrant overriding the algorithm. [ABSTRACT FROM AUTHOR]

Chromosomal integration of genome-intact HIV-1 sequences into the host genome creates a reservoir of virally infected cells that persists throughout life, necessitating indefinite antiretroviral suppression therapy. During effective antiviral treatment, the majority of these proviruses remain transcriptionally silent, but mechanisms responsible for viral latency are insufficiently clear. Here, we used matched integration site and proviral sequencing (MIP-Seq), an experimental approach involving multiple displacement amplification of individual proviral species, followed by near-full-length HIV-1 next-generation sequencing and corresponding chromosomal integration site analysis to selectively map the chromosomal positions of intact and defective proviruses in 3 HIV-1-infected individuals undergoing long-term antiretroviral therapy. Simultaneously, chromatin accessibility and gene expression in autologous CD4+ T cells were analyzed by assays for transposase-accessible chromatin using sequencing (ATAC-Seq) and RNA-Seq. We observed that in comparison to proviruses with defective sequences, intact HIV-1 proviruses were enriched for non-genic chromosomal positions and more frequently showed an opposite orientation relative to host genes. In addition, intact HIV-1 proviruses were preferentially integrated in either relative proximity to or increased distance from active transcriptional start sites and to accessible chromatin regions. These studies strongly suggest selection of intact proviruses with features of deeper viral latency during prolonged antiretroviral therapy, and may be informative for targeting the genome-intact viral reservoir. [ABSTRACT FROM AUTHOR]

The article presents case study of a 68-year-old woman who was diagnosed with Indian tick typhus caused by Rickettsia conorii subspecies indica. It mentions that Rickettsia conorii subspecies indica was associated with diarrhea, altered mental status, hyponatremia, arthralgias without arthritis, and a mild cough with normal findings on a cardiopulmonary examination and chest radiography.

Background: Differences between the designs of hepatitis C virus (HCV) viral load assays can result in genotyperelated variability in RNA quantification. We tested paired aliquots of plasma specimens from HCV-infected individuals using two versions (v1.0 and v2.0) of the Roche COBAS AmpliPrep/COBAS TaqMan HCV Test (CAP/CTM HCV) and noted variability between results for a subset of specimens; we then sought to determine whether discrepant results were more prevalent among specific HCV genotypes. Methods: Archived and prospectively-collected plasma samples from 114 unique patients were tested using CAP/CTM HCV v1.0 and v2.0. The HCV genotype result for each patient was determined by retrospectively reviewing laboratory records. Results: All (46/46) specimens with quantifiable viral loads from patients with genotype 1 or 2 infection had CAP/CTM HCV v1.0 and v2.0 results that were within 0.5 log10 IU/mL; in contrast, only 3/11 (27.3%) from patients with HCV genotype 3 (mean difference, 0.56 log10 IU/mL higher with v2.0) and 0/3 (0%) from patients with HCV genotype 4 (mean difference, 0.91 log10 IU/mL higher with v2.0) had results within 0.5 log10 IU/mL. Among specimens with detectable HCV RNA below the lower limit of quantification with v1.0, greater proportions of genotype 3 (4/7, 57.1%) and genotype 4 (3/4, 75.0%) specimens than genotype 1 or 2 specimens (6/30, 20.0%) had v2.0 results within the quantifiable range. Conclusions: In patients infected with HCV genotype 3, sequential CAP/CTM HCV viral load results should be compared with caution and interpreted in the context of the specific assay version used. [ABSTRACT FROM AUTHOR]

HIV-1 causes a chronic, incurable disease due to its persistence in CD4+ T cells that contain replication-competent provirus, but exhibit little or no active viral gene expression and effectively resist combination antiretroviral therapy (cART). These latently infected T cells represent an extremely small proportion of all circulating CD4+ T cells but possess a remarkable long-term stability and typically persist throughout life, for reasons that are not fully understood. Here we performed massive single-genome, near-full-length next-generation sequencing of HIV-1 DNA derived from unfractionated peripheral blood mononuclear cells, ex vivo-isolated CD4+ T cells, and subsets of functionally polarized memory CD4+ T cells. This approach identified multiple sets of independent, near-full-length proviral sequences from cART-treated individuals that were completely identical, consistent with clonal expansion of CD4+ T cells harboring intact HIV-1. Intact, near-full-genome HIV-1 DNA sequences that were derived from such clonally expanded CD4+ T cells constituted 62% of all analyzed genome-intact sequences in memory CD4 T cells, were preferentially observed in Th1-polarized cells, were longitudinally detected over a duration of up to 5 years, and were fully replication- and infection-competent. Together, these data suggest that clonal proliferation of Th1-polarized CD4+ T cells encoding for intact HIV-1 represents a driving force for stabilizing the pool of latently infected CD4+ T cells. [ABSTRACT FROM AUTHOR]

HIV-1 is able to evade innate antiviral responses during acute infection to establish a chronic systemic infection which, in the absence of antiretroviral therapy (ART), typically progresses to severe immunodeficiency. Understanding these early innate immune responses against HIV-1 and their mechanisms of failure is relevant to the development of interventions to better prevent HIV-1 transmission. Human beta defensins (HBDs) are antibacterial peptides but have recently also been associated with control of viral replication. HBD1 and 2 are expressed in PBMCs as well as intestinal tissue, but their expression in vivo during HIV-1 infection has not been characterized. We demonstrate that during acute HIV-1 infection, HBD1 but not HBD2 is highly upregulated in circulating monocytes but returns to baseline levels during chronic infection. HBD1 expression in monocytes can be induced by HIV-1 in vitro, although direct infection may not entirely account for the increase in HBD1 during acute infection. We provide evidence that HIV-1 triggers antiviral IFN-α responses, which act as a potent inducer of HBD1. Our results show the first characterization of induction of an HBD during acute and chronic viral infection in humans. HBD1 has been reported to have low activity against HIV-1 compared to other defensins, suggesting that in vivo induced defensins may not significantly contribute to the robust early antiviral response against HIV-1. These data provide important insight into the in vivo kinetics of HBD expression, the mechanism of HBD1 induction by HIV-1, and the role of HBDs in the early innate response to HIV-1 during acute infection. [ABSTRACT FROM AUTHOR]

Due to the stringent population bottleneck that occurs during sexual HIV-1 transmission, systemic infection is typically established by a limited number of founder viruses. Elucidation of the precise forces influencing the selection of founder viruses may reveal key vulnerabilities that could aid in the development of a vaccine or other clinical interventions. Here, we utilize deep sequencing data and apply a genetic distance-based method to investigate whether the mode of sexual transmission shapes the nascent founder viral genome. Analysis of 74 acute and early HIV-1 infected subjects revealed that 83% of men who have sex with men (MSM) exhibit a single founder virus, levels similar to those previously observed in heterosexual (HSX) transmission. In a metadata analysis of a total of 354 subjects, including HSX, MSM and injecting drug users (IDU), we also observed no significant differences in the frequency of single founder virus infections between HSX and MSM transmissions. However, comparison of HIV-1 envelope sequences revealed that HSX founder viruses exhibited a greater number of codon sites under positive selection, as well as stronger transmission indices possibly reflective of higher fitness variants. Moreover, specific genetic “signatures” within MSM and HSX founder viruses were identified, with single polymorphisms within gp41 enriched among HSX viruses while more complex patterns, including clustered polymorphisms surrounding the CD4 binding site, were enriched in MSM viruses. While our findings do not support an influence of the mode of sexual transmission on the number of founder viruses, they do demonstrate that there are marked differences in the selection bottleneck that can significantly shape their genetic composition. This study illustrates the complex dynamics of the transmission bottleneck and reveals that distinct genetic bottleneck processes exist dependent upon the mode of HIV-1 transmission. [ABSTRACT FROM AUTHOR]