Lymphocytic Choriomeningitis Virus in Person Living with HIV, Connecticut, USA, 2021.

Lymphocytic choriomeningitis virus is an underreported cause of miscarriage and neurologic disease. Surveillance remains challenging because of nonspecific symptomatology, inconsistent case reporting, and difficulties with diagnostic testing. We describe a case of acute lymphocytic choriomeningitis virus disease in a person living with HIV in Connecticut, USA, identified by using quantitative reverse transcription PCR.

Electronic Health Record-Assisted Reflex Urine Culture Testing Improves Emergency Department Diagnostic Efficiency.

The authors evaluated the effectiveness of an electronic health record (EHR)-based reflex urine culture testing algorithm on urine test utilization and diagnostic yield in the emergency department (ED). The study implemented a reflex urine culture order with EHR decision support. The primary outcome was the number of urine culture orders per 100 ED visits. The secondary outcome was the diagnostic yield of urine cultures. After the intervention, the mean number of urine cultures ordered was 5.95 fewer per 100 ED visits (9.3 vs 15.2), and there was a decrease in normal, or negative, cultures by 2.42 per 100 ED visits. There also was a statistically significant decrease in urine culture utilization and an increase in the positive proportion of cultures. Simple EHR clinical decision-support tools along with reflex urine culture testing can significantly reduce the number of urine cultures performed while improving diagnostic yield in the ED.

Graft loss among renal-transplant recipients with early reduction of immunosuppression for BK viremia.

AIM: To review the incidence of graft loss and acute rejection among renal transplant recipients with early reduction of immunosuppression for BK viremia. METHODS: We performed a retrospective analysis of consecutive de-novo kidney-only transplants from January 2009 to December 2012 to evaluate the incidence of Polyoma-virus associated nephropathy (PyVAN). Recipient plasma was screened for BKV DNA via quantitative polymerase chain reaction (PCR) at months 1, 3, 6, 9 and 12 post-transplant and on worsening graft function. Immunosuppression was reduced at ≥ 3-log copies/mL. Those with viremia of ≥ 4-log copies/mL (presumptive PyVAN) underwent renal transplant biopsy. Presumptive PyVAN (PP) and definitive PyVAN (DP; biopsy-proven) were treated by immunosuppression reduction (IR) only. RESULTS: Among 319 kidney transplant recipients, the median age was 53 years (range 19-83), 65.8% were male, and 58.9% were white. Biopsy-proven acute rejection was found in 18.5% within 0-168 wk. Death-censored graft loss occurred in 5.3% (n = 17) and graft loss attributable to PyVAN was 0.6% (n = 2). Forty-seven patients were diagnosed with PP (14.7%) and 18 (5.6%) with DP. Graft loss among participants with PyVAN (8.5%) and those without (4.8%) was not significantly different. Deceased donor kidney transplantation (OR = 2.3, 95%CI = 1.1-4.6) and AR (OR = 2.3, 95%CI = 1.2-4.7) were associated with PyVAN in the multivariate analysis. BK viremia between 3 and 4-log copies/mL occurred in 27 patients, all of whom underwent IR. Of these, 16 (59%) never developed PyVAN while 11 (41%) developed PyVAN (4 DP, 7 PP) within a range of 11-39 wk. CONCLUSION: Instituting an early reduction of immunosuppression, in the absence of adjunctive antivirals, is effective at preventing PyVAN and may be associated with a lower incidence of graft-loss without a reciprocal increase in the incidence of acute rejection.

Laboratory Diagnosis of Zika Virus Infection.

CONTEXT: -The rapid and accurate diagnosis of Zika virus infection is an international priority. OBJECTIVE: -To review current recommendations, methods, limitations, and priorities for Zika virus testing. DATA SOURCES: -Sources include published literature, public health recommendations, laboratory procedures, and testing experience. CONCLUSIONS: -Until recently, the laboratory diagnosis of Zika infection was confined to public health or research laboratories that prepared their own reagents, and test capacity has been limited. Furthermore, Zika cross-reacts serologically with other flaviviruses, such as dengue, West Nile, and yellow fever. Current or past infection, or even vaccination with another flavivirus, will often cause false-positive or uninterpretable Zika serology results. Detection of viral RNA during acute infection using nucleic acid amplification tests provides more specific results, and a number of commercial nucleic acid amplification tests have received emergency use authorization. In addition to serum, testing of whole blood and urine is recommended because of the higher vial loads and longer duration of shedding. However, nucleic acid amplification testing has limited utility because many patients are asymptomatic or present for testing after the brief period of Zika shedding has passed. Thus, the greatest need and most difficult challenge is development of accurate antibody tests for the diagnosis of recent Zika infection. Research is urgently needed to identify Zika virus epitopes that do not cross-react with other flavivirus antigens. New information is emerging at a rapid pace and, with ongoing public-private and international collaborations and government support, it is hoped that rapid progress will be made in developing robust and widely applicable diagnostic tools.

Characterizing Patients with Very-Low-Level HIV Viremia: A Community-Based Study.

OBJECTIVE: Very-low-level viremia (VLLV) is a relatively new concept in the realm of human immunodeficiency virus (HIV) care. Newer generation assays are now able to detect plasma HIV RNA Viral Load (VL) levels as low as 20 copies/mL. The authors characterized patients with VLLV (VL between 20 and 50 copies/mL) in order to identify possible risk factors associated with virologic failure and poor clinical outcomes. METHODS: The authors reviewed 119 consecutive charts of patients with VLLV. Sociodemographic data were extracted and viral load and CD4 counts were trended over a 12 month period (February 2013-February 2014). Regression analysis was used to assess the role of different factors on virologic failure at 1 year. RESULTS: Of the study participants with evaluable data (n = 100), the median age was 53 years (interquartile range: 43-57.5), 67% were nonwhite, 34% were women, 58% were smokers, 47% were alcoholics, 58% had a history of intravenous drug use, and 40% were coinfected with hepatitis C virus. More than half of the participants had 3 or more comorbidities and their HIV pill burden was high (more than 2 pills daily). After 12 months, 65 participants achieved undetectable viral load levels, whereas 15 experienced virologic failure (2 consecutive viral loads > 50 copies/mL) and the remaining 20 had persistent VLLV. In the virologic failure group, there was a predominance of white males (66%) with a significant number of comorbidities and pill burden. Univariate logistic regression suggested that there was a difference between the failure versus nonfailure groups in terms of race, ethnicity, and alcohol use. Multivariate regression with virological failure as the outcome suggested a trend only in terms of participant's alcohol use. CONCLUSION: Most patients with initial VLLV (70%) achieved virologic suppression at 1 year with no antiretroviral therapy changes. Thus, VLLV does not necessarily predict virologic failure and should not prompt more frequent clinic visits or antiretroviral regimen changes. Further research is needed in order to determine the predictors of virologic failure in this subset of patients and the clinicians' attitude toward VLLV.

Parvovirus B19.

Primary parvovirus B19 infection is an infrequent, but serious and treatable, cause of chronic anemia in immunocompromised hosts. Many compromised hosts have preexisting antibody to B19 and are not at risk. However, upon primary infection, some patients may be able to mount a sufficient immune response to terminate active parvovirus B19 infection of erythroid precursors. The most common consequence of B19 infection in the compromised host is pure red-cell aplasia, resulting in chronic or recurrent anemia with reticulocytopenia. Anemia persists until neutralizing antibody is either produced by the host or passively administered. Parvovirus B19 should be suspected in compromised hosts with unexplained or severe anemia and reticulocytopenia, or when bone-marrow examination shows either giant pronormoblasts or absence of red-cell precursors. Diagnosis is established by detection of B19 DNA in serum in the absence of IgG antibody to B19. In some cases, IgG antibody is detected but is not neutralizing. Anti-B19 IgM may or may not be present. Therapy includes any or all of the following: red-cell transfusion, adjustment in medications to restore or improve the patient's immune system, and administration of intravenous immunoglobulin (IVIG). Following treatment, patients should be closely monitored, especially if immunosuppression is unchanged or increased. Should hematocrit trend downward and parvovirus DNA trend upward, the therapeutic options above should be revisited. In a few instances, monthly maintenance IVIG may be indicated. Caregivers should be aware that B19 variants, though rarely encountered, can be missed or under-quantitated by some real-time polymerase-chain reaction methods.

Immunoglobulin M for Acute Infection: True or False?

Immunoglobulin M (IgM) tests have clear clinical utility but also suffer disproportionately from false-positive results, which in turn can lead to misdiagnoses, inappropriate therapy, and premature closure of a diagnostic workup. Despite numerous reports in the literature, many clinicians and laboratorians remain unaware of this issue. In this brief review, a series of virology case examples is presented. However, a false-positive IgM can occur with any pathogen. Thus, when an accurate diagnosis is essential for therapy, prognosis, infection control, or public health, when the patient is sick enough to be hospitalized, or when the clinical or epidemiologic findings do not fit, IgM detection should not be accepted as a stand-alone test. Rather, whenever possible, the diagnosis should be confirmed by other means, including testing of serial samples and the application of additional test methods.

Atypical hand-foot-and-mouth disease associated with coxsackievirus A6 infection.

BACKGROUND: Hand-foot-and-mouth disease (HFMD) is an acute viral illness commonly caused by coxsackievirus (CV)-A16 and enterovirus 71 infections. Recently, atypical HFMD has been reported in association with CV-A6, an uncommon enterovirus strain. OBJECTIVE: We sought to describe the clinical features of atypical HFMD associated with CV-A6 infection and its diagnostic laboratory evaluation. METHODS: Patients presenting to our institution with history and examination suggestive of atypical HFMD from January 2012 to July 2012 were identified. Morphology and distribution of mucocutaneous lesions were recorded. Enterovirus infection was assessed by reverse transcriptase polymerase chain reaction of biologic specimens. Enterovirus type was determined by viral capsid protein 1 gene sequencing. RESULTS: Two adults and 3 children with atypical HFMD were identified. Four of 5 patients exhibited widespread cutaneous lesions. In 2 patients with a history of atopic dermatitis, accentuation in areas of dermatitis was noted. Associated systemic symptoms prompted 4 of 5 patients to seek emergency care, and both adults were hospitalized for diagnostic evaluation. Infection with CV-A6 was confirmed in all patients. LIMITATIONS: This study is a case series from a single institution. CONCLUSION: Consideration of the expanded range of cutaneous findings in atypical HFMD caused by CV-A6 infection may assist clinicians in diagnosis and management.

Diagnostic tests for influenza infection.

PURPOSE OF REVIEW: The 2009 H1N1 pandemic focused attention on the speed and accuracy of influenza diagnostic methods. This review provides an update on current tests and new developments. RECENT FINDINGS: Widely used rapid antigen tests and immunofluorescence tests were generally less sensitive for 2009 H1N1 influenza than for seasonal influenza. In addition, marked variability was reported for the same tests in different settings and patient groups. The advantages of molecular testing gained wide recognition, namely high sensitivity, speed compared with culture, ability to assess viral load and to identify subtype. Although adoption of influenza molecular testing can be expected to accelerate, immunoassays and rapid cultures performed on site retain advantages for many facilities. Falsely negative results were seen with all methods, especially for samples collected very early or late. SUMMARY: Influenza diagnostic test performance can be adversely affected by viral genetic and antigenic changes and should be re-assessed annually. Variability in sensitivity and specificity of the same test in different settings highlights the need for each laboratory to ensure optimal procedures and work with clinicians to improve sample quality. Manufacturers have been motivated to improve immunoassays and develop simpler and faster multiplex molecular tests, hopefully in advance of the next pandemic.

Developments in immunologic assays for respiratory viruses.

In most hospitals, clinics, and doctor's offices, immunologic assays are the only tests performed on site for the diagnosis of respiratory viruses. More than other methods, immunoassays have been shown to affect patient management and save costs, aiding early administration of antiviral therapy, reduction in unnecessary tests and antibiotics, and earlier discharges. This article discusses the major immunologic methods employed for respiratory virus diagnosis, recent developments in immunoassays and sample collection, and current test algorithms.

CSF IgH gene rearrangement analysis in isolated post-transplant lymphoproliferative disorder of the central nervous system.

Isolated post-transplant lymphoproliferative disorder (PTLD) of the central nervous system is rare and its diagnosis can be challenging. A biopsy is usually required in order to distinguish the disease from opportunistic infections. We present a case in whom immunoglobulin heavy chain gene rearrangement analysis of cerebrospinal fluid (CSF) was instrumental in establishing the diagnosis.

Rapid HIV testing of women in labor: too long a delay.

For HIV-infected women who have not received antiretroviral treatment or transmission prophylaxis in pregnancy, starting antiretrovirals in labor or soon after birth can still decrease the risk of perinatal transmission. There is, therefore, potential benefit in conducting rapid HIV testing in labor, but hospitals are seldom prepared to conduct such testing. We compared protocols for rapid HIV testing at 2 hospitals to determine what proportion of women had results back early enough to intervene if results had been positive. Hospital A initially used HIV enzyme-linked immunosorbent assays (ELISAs) and changed to using rapid tests (eg, Single Use Diagnostic System [SUDS]); hospital B used only the SUDS. With use of the SUDS in hospital A, results were reported more quickly than with the ELISA protocol in the same hospital (P < 0.0001). Comparing use of the SUDS in the 2 hospitals, test results were available more quickly in hospital A than hospital B (P < 0.05), which resulted in hospital A having more results reported prior to delivery (64% vs. 38%, P < 0.05) and within 12 hours postdelivery (94% vs. 73%, P < 0.05). If HIV testing in labor is to have its maximum effect on decreasing the risk of perinatal HIV transmission, hospitals need to institute rapid HIV testing, but protocols must ensure that results are available as quickly as possible.