The Emergence of Streptococcus anginosus Group as a Cystic Fibrosis Pathogen

Molecular profiling studies have identified potential emerging pathogens, such as Streptococcus anginosus group, that may play a role in cystic fibrosis (CF) lung disease by either directly causing infection or upregulating the virulence factors of classic CF pathogens, such as Pseudomonas aeruginosa. Routine surveillance of CF pathogens using traditional microbiology culture guides treatment and management of CF patients; however, routine CF culture protocols have not been modified to select for, detect, and further determine the role these emerging pathogens play in the progression of CF lung disease.     

Rapid diagnostic tests for infectious diseases in the emergency department

BackgroundRapid diagnostic tests (RDTs) for infectious diseases, with a turnaround time of less than 2 hours, are promising tools that could improve patient care, antimicrobial stewardship and infection prevention in the emergency department (ED) setting. Numerous RDTs have been developed, although not necessarily for the ED environment. Their successful implementation in the ED relies on their performance and impact on patient management.ObjectivesThe aim of this narrative review was to provide an overview of currently available RDTs for infectious diseases in the ED.SourcesPubMed was searched through August 2019 for available studies on RDTs for infectious diseases. Inclusion criteria included: commercial tests approved by the US Food and Drug Administration (FDA) or Conformité Européenne (CE) in vitro diagnostic devices with data on clinical samples, ability to run on fully automated systems and result delivery within 2 hours.ContentA nonexhaustive list of representative commercially available FDA- or CE-approved assays was categorized by clinical syndrome: pharyngitis and upper respiratory tract infection, lower respiratory tract infection, gastrointestinal infection, meningitis and encephalitis, fever in returning travellers and sexually transmitted infection, including HIV. The performance of tests was described on the basis of clinical validation studies. Further, their impact on clinical outcomes and anti-infective use was discussed with a focus on ED-based studies.ImplicationsClinicians should be familiar with the distinctive features of each RDT and individual performance characteristics for each target. Their integration into ED work flow should be preplanned considering local constraints of given settings. Additional clinical studies are needed to further evaluate their clinical effectiveness and cost-effectiveness.     

Aerococcus urinae,Alloscardovia omnicolens, and Actinotignum schaalii: the AAA Minor League Team of Urinary Tract Infection Pathogens

In clinical microbiology laboratories, advancements in the methods used for routine organism identification have facilitated more accurate species level resolution. This, along with increasing knowledge regarding “new” pathogens, has provided new insights into biology and has revealed clinical associations not previously known. Aerococcus urinae, Alloscardovia omnicolens, and Actinotignum schaalii are Gram-positive bacteria associated with urinary tract infections but can also be members of the urinary tract microbiota. In addition, invasive infections have been reported for the three bacteria, usually with a urinary tract source. Importantly, the use of routine biochemical testing methods for identification of these bacteria can result in misidentification or the incorrect determination that they are not clinically significant. Of these bacteria, only A. urinae has antimicrobial susceptibility testing criteria and interpretative breakpoints. Microbiologists and clinicians need to be aware of these urinary tract pathogens and how to correctly identify them.     

“Did I Hear You Correctly? The Organism Identified Was Corynebacterium diphtheriae?”

Diphtheria is a bacterial infection caused by Corynebacterium diphtheriae and is primarily transmitted from person to person through close physical and respiratory contact; disease can involve almost any mucous membrane and is classified depending on the anatomic site of infection. Diphtheria is an acute, toxin-mediated disease whose occurrence is characterized by periodicity and epidemic waves, with a high incidence and mortality. Once one of the leading causes of childhood death, global diphtheria incidence declined approximately 70% through implementation of widespread vaccination programs. However, a major epidemic of diphtheria occurred during the 1990s in the Russian Federation and the newly independent states of the former Soviet Union. Although the epidemic is under control, toxigenic C. diphtheriae strains are still reported in Europe and globally, including North and South America, the Indian subcontinent, Africa, Southeast Asia, and the eastern Mediterranean. Rapid clinical and public health responses are required to control diphtheria outbreaks, with the clinical microbiology laboratory playing an essential role in providing prompt and rapid identification. In light of experience with a recent case of nontoxigenic C. diphtheriae respiratory infection, aspects of this organism and the diseases it causes are reviewed.     

Rapid diagnostic tests for determining dengue serostatus: a systematic review and key informant interviews

ObjectivesVaccination for dengue with the live attenuated tetravalent CYD-TDV vaccine (Dengvaxia®) is only recommended in individuals who have had prior dengue virus (DENV) infection. Rapid diagnostic tests (RDT) for past DENV infection would offer a convenient method for pre-vaccination screening at point-of-care. A systematic review was conducted to evaluate the performance of current dengue RDTs for determining dengue serostatus, using IgG antibodies against DENV as a marker of past infection.MethodsPubMed and EMBASE databases were searched from 2000 to 2018 to identify studies evaluating dengue RDTs in individuals with known or possible previous DENV infection. Study quality was evaluated using GRADE and QUADAS-2 criteria. Semi-structured interviews were also performed with available dengue RDT manufacturers.ResultsThe performance of four dengue IgG RDTs was determined in 3137 individuals across ten studies conducted in 13 countries, with serum used in most of the studies. No studies reported data for determining dengue serostatus, and limited data were available regarding cross-reactivity with other viruses. The majority of studies demonstrated sensitivities and specificities between 80% and 100% for dengue IgG detection in samples from secondary infection or convalescent time-points after recent infection.ConclusionsAlthough current dengue IgG RDTs have shown reasonable performance compared with laboratory-based tests in secondary infection, additional research is needed to determine how RDTs would perform in relevant populations targeted for vaccination. New RDTs or modifications to current RDTs are feasible and may optimize the performance of these tests for use in a pre-vaccination screening approach.     

Wohlfahrtiimonas chitiniclastica: Two Clinical Cases and a Review of the Literature

Wohlfahrtiimonas chitiniclastica has been identified as an emerging pathogen predominantly associated with cutaneous myiasis and poor hygiene. Traditional biochemical methods can be unreliable and misleading when identifying this organism, and modern molecular techniques are often necessary for high-confidence identification. There have been very few cases of human infection with W. chitiniclastica reported in the literature. We present two recent cases identified at the University of Kentucky Medical Center (a male with myiasis related to gangrene and an elderly female with a left-leg wound and myiasis), both of which were identified using matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) for identification, and describe the clinical and microbiologic characteristics associated with this microorganism.     

Rickettsioses in the United States

Rickettsiae are obligate intracellular Gram-negative bacilli with global distribution. In the United States, nine Rickettsia species have been reported to cause disease in humans and are collectively responsible for the thousands of rickettsioses reported each year. Rickettsial infections are transmitted to humans via a variety of arthropod vectors, including ticks, lice, fleas, and mites. The severity of human infection ranges from subclinical and mild to severe and life threatening, dependent upon the infecting Rickettsia species, host factors, and time to appropriate antimicrobial therapy. Clinical presentation is often non-specific, making early recognition a challenge for health care professional. Awareness and appreciation of rickettsial pathogens is key to early diagnosis and prompt treatment.     

Clinical predictors of the leading pathogens in human immunodeficiency virus-infected adults with community-onset bacteremia in the emergency department: The importance of transmission routes

Background/Purpose

To investigate the clinical characteristics and pathogens of community-onset bacteremia among human immunodeficiency virus (HIV)-infected adults as well as to establish the clinical predictors of the major microorganisms.

Comparative Evaluation of 11 Commercialized Rapid Diagnostic Tests for Detecting Trypanosoma cruzi Antibodies in Serum Banks in Areas of Endemicity and Nonendemicity

Chagas disease is one of the main public health issues in Latin America. Increasingly during the past few decades, Trypanosoma cruzi infection has been detected in North America, Europe, and the Western Pacific, mainly as a result of population movement. The limited availability of rapid serological diagnostic tests hinders rapid diagnosis and early treatment in areas of endemicity and nonendemicity. In collaboration with 11 national reference laboratories (NRLs) from different geographical areas, we evaluated the performances of commercialized serological rapid diagnostic tests (RDT) for T. cruzi infection. Eleven commercialized T. cruzi infection RDTs were evaluated on a total of 474 samples extensively tested with at least three different techniques for Chagas disease, maintained at controlled low temperatures, and stored in the serum banks of the 11 NRLs. We measured the sensitivity, specificity, and concordance of each RDT and provided an additional questionnaire to evaluate its ease of use. The selected RDTs in this study were performed under controlled laboratory conditions. Out of the 11 RDTs, we found 8 of them to be useful, with the cassette format favored over the strip. We did not observe significant differences in RDT performances in the different regions. Overall, the performance results were lower than those disclosed by the manufacturers. The results of this evaluation validate the possibility of using RDTs to diagnose Chagas disease, thereby decreasing the time to treatment at a primary health care facility for patients who are willing to be treated. Further studies should be conducted in the laboratory and in the field to confirm these data, expressly to evaluate reproducibility in resource-limited settings, or using whole blood in clinical settings in areas of endemicity and nonendemicity.     

Fusarium spp., a Genus of Common Plant Pathogens That Can Cause Devastating,Opportunistic Human Disease

Fusarium spp. are environmental hyaline molds that are pathogens in plants and opportunistic pathogens in humans. In immunocompetent individuals, Fusarium sp. infections primarily include keratitis, onychomycosis, and localized infections due to trauma. However, in immunocompromised patients, particularly those with hematological malignancies, members of this genus can cause devastating, invasive, and disseminated infections with high mortality. In general, these species are resistant to therapy with a variety of antifungal agents. This article reviews recent literature about human infections caused by Fusarium spp., treatment and outcomes, and methods for accurately identifying isolates recovered from clinical specimens.     

Malaria rapid diagnostic tests in travel medicine

Malaria is a serious condition in the non-immune traveller, and prognosis depends on timely diagnosis. Although microscopy remains the cornerstone of diagnosis, malaria rapid diagnostic tests (RDTs) are increasingly used in non-endemic settings. They are easy to use, provide results rapidly and require no specific training and equipment. Reported sensitivities vary between different RDT products but are generally good for Plasmodium falciparum, with RDTs detecting the P. falciparum antigen histidine-rich protein-2 (PfHRP2) scoring slightly better than P. falciparumlactate dehydrogenase (Pf-pLDH)-detecting RDTs. Sensitivity is lower for Plasmodium vivax (66.0 – 88.0%) and poor for Plasmodium ovale (5.5 – 86.7%) and Plasmodium malariae (21.4 – 45.2%). Rapid diagnostic tests have several other limitations, including persistence of the PfHRP2 antigen, cross-reactions of P. falciparum with the non-falciparum test line and vice versa and (rare) false-positive reactions due to other infectious agents or immunological factors. False-negative results occur in the case of low parasite densities, prozone effect or pfhrp2 gene deletions. In addition, errors in interpretation occur, partly due to inadequacies in the instructions for use. Finally, RDTs do not give information about parasite density. In the diagnostic laboratory, RDTs are a valuable adjunct to (but not a replacement for) microscopy for the diagnosis of malaria in the returned traveller.In malaria endemic settings, special groups of travellers (those travelling for long periods, expatriates and short-stay frequent travellers) who are remote from qualified medical services may benefit from self-diagnosis by RDTs, provided they use correctly stored RDT products of proven accuracy, with comprehensive instructions for use and appropriate hands-on training.     

Point-of-Care Testing for Group A Streptococcus Infection and Influenza

Point of care (POC) testing has emerged as a critical tool in the early and rapid diagnosis and treatment of infectious diseases. While the mainstay of these POC tests has been lateral-flow-based antigen detection assays, recent technological advances in nucleic acid detection combined with regulatory changes has allowed more sensitive detection of infectious etiologies in the near-patient setting. This advancement is particularly impactful in the ambulatory setting, where rapid diagnosis can ensure appropriate treatment at the early stages of infection, both preventing more serious sequelae and also improving physician workflow and patient satisfaction. Along with this new technology come concerns about quality of testing, nucleic acid contamination, and the appropriate use of POC tests. This review covers the clinical manifestations of disease, the current state of POC testing, and the impact of molecular testing for both group A Streptococcus infection and influenza.     

Self-Collected Specimens for Infectious Disease Testing

Self-collected specimens for infectious disease testing are becoming more commonplace. There are multiple published studies demonstrating that self-collected vaginal swabs for detection of sexually transmitted pathogens are as accurate as physician-collected endocervical swabs. Similarly, self-collected penile-meatal swabs are also acceptable for detecting sexually transmitted pathogens; however, unlike self-collected vaginal swabs, penile-meatal swabs are not considered an “on-label” specimen for U.S. FDA-cleared in vitro diagnostic products. Data on the accuracy of self-collected nasal specimens for respiratory tract infections are encouraging, but studies also show that patients do not always follow instructions when mailing samples back to the laboratory. Unfortunately, there are only a few reports of self-collected specimens for detecting enteric pathogens, such as Salmonella, Shigella, or Campylobacter. Microbiologists need to be proactive in making sure that training materials developed for self-collection (such as laminated cards, videos, and other resources) are accurate and easy to understand (which includes being available in multiple languages) and provide clear instructions on how to handle a specimen once it has been collected.     

Accuracy of cholera rapid diagnostic tests: a systematic review and meta-analysis

BackgroundCholera is an acute diarrheal disease caused by Vibrio cholerae O1 or O139. Cholera rapid diagnostic tests (RDTs) are widely used to screen for cholera cases. However, their accuracy has not been systematically reviewed.ObjectivesTo evaluate the diagnostic accuracy of cholera RDTs.MethodsSystematic review and meta-analysis.Data sourcesMedline, EMBASE and Web of science through to November 2020; references of included studies and a technical guidance on cholera RDTs. This review is registered with PROSPERO (CRD42021233124).Study eligibility criteriaCross-sectional studies comparing the performance of cholera RDTs either to stool culture or PCR.ParticipantsIndividuals with clinically suspected cholera.Data extractionTwo authors independently extracted data and assessed the quality using Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) criteria.ResultsEighteen studies were included in the systematic review of which 17 were used for meta-analysis. Crystal VC was the most frequently used RDT (13 studies), followed by Cholkit and Institut Pasteur cholera dipstick (three studies each), SD Bioline (two studies), Artron (one study) and Smart (one study). Using direct testing (n = 12 627 specimens), the bivariate random-effects model yielded a pooled sensitivity and specificity of 91% (95% CI 87%–94%) and 80% (95% CI 74%–84%), respectively. However, through alkaline peptone water (APW) enrichment (n = 3403 specimens), the pooled sensitivity and specificity were 89% (95% CI 79%–95%) and 98% (95% CI 95%–99%), respectively.ConclusionCholera RDTs, especially when enriched with APW, have moderate sensitivity and specificity. Although less useful for clinical management, the current generation of RDTs have clear utility for surveillance efforts if used in a principled manner. Enrichment of stool specimens in APW before using cholera RDTs reduces the possibility of obtaining false-positive results, despite the few cholera cases that go undetected. It is noteworthy that APW-enriched cholera RDTs are not necessarily rapid tests, and are not listed in the Global Task Force on Cholera Control/WHO target product profile.     

Candida auris for the Clinical Microbiology Laboratory: Not Your Grandfather's Candida Species

Candida auris is a newly emerging species that was first identified in Asia in 2009 but has rapidly spread across the world. C. auris differs from most other Candida species in that antifungal resistance is the norm rather than the exception, it is a commensal of human skin rather than the human gut, and it can be easily transmitted from person to person in a health care setting. This review discusses the emergence of C. auris, global epidemiology, identification, antifungal susceptibility testing, and precautions to be taken when it is identified from a patient specimen.     

Genetic diversity and deletion of Plasmodium falciparum histidine-rich protein 2 and 3: a threat to diagnosis of P. falciparum malaria

BackgroundPfHRP2-based rapid diagnostic tests (RDTs), based on the recognition of the Plasmodium falciparum histidine-rich protein 2, are currently the most used tests in malaria detection. Most of the antibodies used in RDTs also detect PfHRP3. However, false-negative results were reported. Significant variation in the pfhrp2 gene could lead to the expression of a modified protein that would no longer be recognized by the antibodies used in PfHRP2-based RDTs. Additionally, parasites lacking the PfHRP2 do not express the protein and are, therefore, not identifiable.AimsThis review aims to assess the pfhrp2 and pfhrp3 genetic variation or the prevalence of gene deletion in areas where malaria is endemic and describe its implications on RDT use.SourcesPublications of interest were identified using PubMed, Google Scholar and Google.ContentMore than 18 types of amino acid repeats were identified from the PfHRP2 sequences. Sequencing analysis revealed high-level genetic variation in the pfhrp2 and pfhrp3 genes (>90% of variation in Madagascar, Nigeria or Senegal) both within and between countries. However, genetic variation of PfHRP2 and PfHRP3 does not seem to be a major cause of false-negative results. The countries that showed the highest proportions of pfhrp2-negative parasites were Peru (20%–100%) and Guyana (41%) in South America, Ghana (36%) and Rwanda (23%) in Africa. High prevalence of pfhrp2 deletion causes a high rate of false-negatives results.ImplicationsPresence of parasites lacking the pfhrp2 gene may pose a major threat to malaria control programmes because P. falciparum-infected individuals are not diagnosed and properly treated.     

Laboratory Evaluation of Three Rapid Diagnostic Tests for Dual Detection of HIV and Treponema pallidum Antibodies

The performance of three research-use-only, dual HIV and syphilis rapid diagnostic tests (RDTs) was evaluated for 150 patient serum samples and compared to reference HIV and Treponema pallidum antibody detection methods. The RDTs performed comparably, with sensitivities of 93 to 99% and specificities of 97 to 100%. The kappa statistic between the RDTs was 0.95.     

Comparative Evaluation of Blood and Serum Samples in Rapid Immunochromatographic Tests for Visceral Leishmaniasis

Rapid diagnostic tests (RDTs) based on the detection of specific antibodies in serum are commonly used for the diagnosis of visceral leishmaniasis (VL). Several commercial kits are available, and some of them allow the use of whole-blood samples instead of serum. An RDT is much more user-friendly for blood samples than for serum samples. In this study, we examined the sensitivities and specificities of six different commercially available immunochromatographic tests for their accuracy in detecting Leishmania infection in whole blood and serum of parasitologically confirmed VL cases. This study was performed in areas of India and Nepal where VL is endemic. A total of 177 confirmed VL cases, 208 healthy controls from areas of endemicity (EHCs), 26 malaria patients (MP), and 37 tuberculosis (TB) patients were enrolled. The reproducibilities of the blood and serum results and between-reader and between-laboratory results were tested. In India, the sensitivities of all the RDTs ranged between 94.7 and 100.0%, with no significant differences between whole blood and serum. The specificities ranged between 92.4 and 100.0%, except for the specificity of the Onsite Leishmania Ab RevB kit, which was lower (33.6 to 42.0%). No differences in specificities were observed for blood and serum. In Nepal, the sensitivities of all the test kits, for whole-blood as well as serum samples, ranged between 96.3 and 100.0%, and the specificities ranged between 90.1 and 96.1%, again with the exception of that of the Onsite Leishmania Ab RevB test, which was markedly lower (48.7 to 49.3%). The diagnostic accuracies of all the tests, except for one brand, were excellent for the whole-blood and serum samples. We conclude that whole blood is an adequate alternative for serum in RDTs for VL, with sensitivities and specificities comparable to those obtained in serum samples, provided that the test kit is of overall good quality.     

Postpartum Streptococcus pyogenes Outbreak in the Labor and Delivery Unit of a Quaternary Referral Center: a Case Series and Review of the Literature

Historically, childbirth was associated with morbidity and mortality, often due to endometritis or puerperal fever. Streptococcus pyogenes was first identified as the cause of puerperal fever by Louis Pasteur, and it remains a virulent and lethal pathogen with a case fatality rate of 15 to 20% [1]. The pathogenesis of postpartum endometritis is believed to be associated with disruption of the woman's mucosal barriers from childbirth and invasion of bacteria either from vaginal flora or from a health care worker's hands [2]. Despite the implementation of hand sanitizing and barrier precautions (gloves), outbreaks of S. pyogenes still occur today [1]. This article provides an overview of the role of S. pyogenes in postpartum infections and describes an outbreak of postpartum endometritis due to S. pyogenes. The case report involved three patients who were admitted to a quaternary care medical center on the same day and, following discharge, were all readmitted with sepsis and endometritis. The bacteria were isolated, and pulsed-field gel electrophoresis revealed that the three S. pyogenes strains were genetically identical.