A Decade of Chronic Norovirus Infection Surveillance at the NIH Clinical Research Center: Clinical Characteristics, Molecular Epidemiology, and Replication.

Background: Noroviruses are an important viral cause of chronic diarrhea in immunocompromised individuals.

Method: We collected norovirus-positive stool samples (n=448) from immunocompromised patients (n=88) at the National Institutes of Health Clinical Research Center, U.S.

Cardiovascular Biomarker Profile on Antiretroviral Therapy Is Not Influenced by History of an IRIS Event in People With HIV and Suppressed Viremia.

Immune reconstitution inflammatory syndrome (IRIS) is characterized by release of proinflammatory cytokines and tissue inflammation occurring early after antiretroviral therapy (ART) initiation. The role of previous IRIS events in persistent chronic inflammation in people with HIV is currently unclear. In this retrospective analysis of 143 participants who maintained suppression of HIV viremia, we compared biomarkers related to inflammation, coagulation, and cardiovascular risk after 3 years on ART in participants with and without a history of IRIS.

Targeted therapy guided by single-cell transcriptomic analysis in drug-induced hypersensitivity syndrome: a case report.

Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DiHS/DRESS) is a potentially fatal multiorgan inflammatory disease associated with herpesvirus reactivation and subsequent onset of autoimmune diseases. Pathophysiology remains elusive and therapeutic options are limited. Cases refractory to corticosteroid therapy pose a clinical challenge and approximately 30% of patients with DiHS/DRESS develop complications, including infections and inflammatory and autoimmune diseases.

Case Report: Ocular toxoplasmosis in a WHIM syndrome immunodeficiency patient.

A patient with WHIM syndrome immunodeficiency presented with sudden painless right eye blindness associated with advanced retinal and optic nerve damage. was detected by PCR in vitreous fluid but not serum.  The patient was treated with pyrimethamine/sulfadiazine for 6 weeks due to evidence of active ocular inflammation and then received prophylaxis with trimethoprim-sulfamethoxazole due to his immunosuppression.

Beyond Blood Smears: Qualification of 18S rRNA as a Biomarker for Controlled Human Malaria Infections.

18S rRNA is a biomarker that provides an alternative to thick blood smears in controlled human malaria infection (CHMI) trials. We reviewed data from CHMI trials at non-endemic sites that used blood smears and 18S rRNA/rDNA biomarker nucleic acid tests (NATs) for time to positivity. We validated a multiplex quantitative reverse transcription-polymerase chain reaction (qRT-PCR) for 18S rRNA, prospectively compared blood smears and qRT-PCR for three trials, and modeled treatment effects at different biomarker-defined parasite densities to assess the impact on infection detection, symptom reduction, and measured intervention efficacy.

High rates of cerebral toxoplasmosis in HIV patients presenting with meningitis in Accra, Ghana.

Background: Data on adult meningitis among patients infected with the human immunodeficiency virus (HIV) is scarce in western sub-Saharan Africa, including Ghana.

Methods: HIV-infected adults with a provisional diagnosis of meningitis were consecutively enrolled, between August 2014 and January 2016. After patient data collection, cerebrospinal fluid (CSF) was obtained and evaluated for microbiological aetiologies, cell counts and biochemistry.

Diagnostic challenges of prolonged post-treatment clearance of Plasmodium nucleic acids in a pre-transplant autosplenectomized patient with sickle cell disease.

Background: Autosplenectomy, as a result of sickle cell disease, is an important risk factor for severe malaria. While molecular methods are helpful in providing rapid and accurate infection detection and species identification, the effect of hyposplenism on result interpretation during the course of infection should be carefully considered.

Case Presentation: A 32-year old autosplenectomized Nigerian male with severe sickle cell disease was referred to the National Institutes of Health for allogenic hematopoietic stem cell transplant.

Pulmonary Infection After Allogeneic Hematopoietic Stem Cell Transplantation: Case Report and Review of the Literature.

Histoplasmosis causes a wide spectrum of clinical illness, including disseminated infection in the immunocompromised. We report a case of pulmonary histoplasmosis in an allogeneic stem cell transplant recipient and review the literature on this topic. Histoplasmosis in this patient population is uncommon, but it is associated with poor outcome.

Epidemiology of Norovirus Infection Among Immunocompromised Patients at a Tertiary Care Research Hospital, 2010-2013.

 Noroviruses are a major cause of infectious gastroenteritis worldwide, and viruses can establish persistent infection in immunocompromised individuals. Risk factors and transmission in this population are not fully understood.  From 2010 through 2013, we conducted a retrospective review among immunocompromised patients (n = 268) enrolled in research studies at the National Institutes of Health Clinical Center and identified a subset of norovirus-positive patients (n = 18) who provided stool specimens for norovirus genotyping analysis.

Protection against malaria at 1 year and immune correlates following PfSPZ vaccination.

An attenuated Plasmodium falciparum (Pf) sporozoite (SPZ) vaccine, PfSPZ Vaccine, is highly protective against controlled human malaria infection (CHMI) 3 weeks after immunization, but the durability of protection is unknown. We assessed how vaccine dosage, regimen, and route of administration affected durable protection in malaria-naive adults. After four intravenous immunizations with 2.

Clinical Performance of Check-Direct CPE, a Multiplex PCR for Direct Detection of bla(KPC), bla(NDM) and/or bla(VIM), and bla(OXA)-48 from Perirectal Swabs.

We evaluated the clinical performance of Check-Direct CPE for carbapenemase detection directly from 301 perirectal swabs (258 patients) in a nonoutbreak setting. Culture of a PCR-confirmed, carbapenemase-containing organism, or history of colonization with such organism within the previous 2 weeks, was used as the reference standard. Check-Direct CPE demonstrated a sensitivity value, specificity value, positive predictive value (PPV), and negative predictive value (NPV) of 100% (all bla(KPC)), 88%, 21%, and 100%, respectively.

First report of Westerdykella dispersa as a cause of an angioinvasive fungal infection in a neutropenic host.

Angioinvasive fungal infections (AFIs) are an important cause of morbidity and mortality among immunocompromised patients. However, clinicomicrobiological characteristics and treatment of many AFI agents remain poorly defined. We report the first human case of infection with Westerdykella dispersa, an emergent cause of AFI, which was successfully treated in a neutropenic pediatric patient.

External quality assurance of malaria nucleic acid testing for clinical trials and eradication surveillance.

Nucleic acid testing (NAT) for malaria parasites is an increasingly recommended diagnostic endpoint in clinical trials of vaccine and drug candidates and is also important in surveillance of malaria control and elimination efforts. A variety of reported NAT assays have been described, yet no formal external quality assurance (EQA) program provides validation for the assays in use. Here, we report results of an EQA exercise for malaria NAT assays.

Protection against malaria by intravenous immunization with a nonreplicating sporozoite vaccine.

Consistent, high-level, vaccine-induced protection against human malaria has only been achieved by inoculation of Plasmodium falciparum (Pf) sporozoites (SPZ) by mosquito bites. We report that the PfSPZ Vaccine--composed of attenuated, aseptic, purified, cryopreserved PfSPZ--was safe and well tolerated when administered four to six times intravenously (IV) to 40 adults. Zero of six subjects receiving five doses and three of nine subjects receiving four doses of 1.

Toward molecular parasitologic diagnosis: enhanced diagnostic sensitivity for filarial infections in mobile populations.

The diagnosis of filarial infections among individuals residing in areas where the disease is not endemic requires both strong clinical suspicion and expert training in infrequently practiced parasitological methods. Recently developed filarial molecular diagnostic assays are highly sensitive and specific but have limited availability and have not been closely evaluated for clinical use outside populations residing in areas of endemicity. In this study, we assessed the performance of a panel of real-time PCR assays for the four most common human filarial pathogens among blood and tissue samples collected from a cohort of patients undergoing evaluation for suspected filarial infections.

Comparison of methods for detection of vaccinia virus in patient specimens.

We analyzed a shell vial culture assay (SVA), real-time PCR, and a direct fluorescent antibody assay (DFA) for rapid detection of vaccinia virus from vaccination sites of Dryvax vaccine recipients. Of 47 samples assayed, 100% were positive by PCR, 89% were positive by SVA, and 40% were positive by DFA. DFA was limited by the need for adequate numbers of cells, with 32% of samples inadequate for interpretation.

Squirrel monkeys support replication of BK virus more efficiently than simian virus 40: an animal model for human BK virus infection.

We performed experiments to test the suitability of squirrel monkeys (Saimiri sciureus) as an experimental model for BK virus (BKV) and simian virus 40 (SV40) infection. Four squirrel monkeys received intravenous inoculation with BKV Gardner strain, and six squirrel monkeys received intravenous inoculation with SV40 777 strain. Eight of 10 monkeys received immunosuppression therapy, namely, cyclophosphamide subcutaneously either before or both before and after viral inoculation.

Clinical trial of quantitative real-time polymerase chain reaction for detection of cytomegalovirus in peripheral blood of allogeneic hematopoietic stem-cell transplant recipients.

The preemptive therapy of cytomegalovirus (CMV) reactivation is useful for the prevention of CMV disease in allogeneic hematopoietic stem-cell transplant (HSCT) recipients. We compared results of the pp65 CMV antigenemia test with quantitative touch-down polymerase chain reaction (Q-PCR) on unfractionated whole blood for the detection of CMV reactivation in 51 HSCT recipients. Forty episodes of reactivation in 28 patients were detected by antigenemia and treated by antiviral drugs.

Florid CD4+, CD56+ T-cell infiltrate associated with Herpes simplex infection simulating nasal NK-/T-cell lymphoma.

We report a case of Herpes simplex virus (HSV) infection of the nasopharynx associated with a dense CD4+, CD56+ T-cell infiltrate that simulated lymphoma on clinical, histologic, and immunophenotypic grounds. Histologic examination showed a tumorlike lymphoid infiltrate with extensive necrosis. Multinucleated giant cells with "ground-glass" nuclei characteristic of HSV were observed in necrotic areas but were not prominent.