Serological Approaches for Trypanosoma cruzi Strain Typing.

Trypanosoma cruzi, the protozoan agent of Chagas' disease, displays a complex population structure made up of multiple strains showing a diverse ecoepidemiological distribution. Parasite genetic variability may be associated with disease outcome, hence stressing the need to develop methods for T. cruzi typing in vivo. Serological typing methods that exploit the presence of host antibodies raised against polymorphic parasite antigens emerge as an appealing approach to address this issue. These techniques are robust, simple, cost-effective, and are not curtailed by methodological/biological limitations intrinsic to available genotyping methods. Here, we critically assess the progress towards T. cruzi serotyping and discuss the opportunity provided by high-throughput immunomics to improve this field.

Serology for Toxoplasma in Immunocompromised Patients: Still Useful?

Toxoplasmosis represents one of the most common comorbidity factors in solid organ or hematopoietic stem cell transplant recipients as well as in other immunocompromised patients. In the past decades, availability and performance of molecular tools for the diagnosis or the exclusion of toxoplasmosis in these patients have greatly improved. However, if accurately used, serology remains a complementary and essential diagnostic tool for physicians and medical parasitologists for the prevention and management of toxoplasmosis in immunocompromised patients as well. It is required for determination of the immunological status of patients against Toxoplasma. It also helps diagnose and monitor complex cases of opportunistic Toxoplasma infection in immunocompromised patients. New perspectives are available to further enhance their yield and ease of use.

Prevalence of Hepatitis B Vaccination Coverage and Serologic Evidence of Immunity Among US-Born Children and Adolescents From 1999 to 2016.

Importance: The World Health Assembly has called for the elimination of hepatitis B and C by 2030. As hepatitis B has no cure, the US strategy to eliminate hepatitis B has focused on prevention through vaccination. However, there are limited data on the trend in vaccine-associated immunity since the US implementation of universal infant hepatitis B vaccination. Objective: To compare self-reported hepatitis B vaccination coverage among children and adolescents with serologic evidence of immunity and infection in the US from 1999 to 2016. Design, Setting, and Participants: This population-based cross-sectional study used data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2016. US-born persons aged 2 to 18 years without missing hepatitis B serologic test results and with reported vaccination history were included. Data were analyzed from September 2017 to June 2018. Main Outcomes and Measures: The proportion of participants who reported complete vaccination for hepatitis B and who had positive serologic test results indicating immunity. Results: Of 21 873 children and adolescents, 51.2%% were male, and the mean (SD) age was 10.6 (4.6) years. The survey reported that hepatitis B vaccination coverage increased significantly from 1999 to 2016 (from 62.6% [95% CI, 58.6%-66.4%] to 86.3% [95% CI, 82.9%-89.2%]; P < .001). Vaccine-associated immunity also increased from 1999 to 2016 among children aged 2 to 5 years (from 60.7% [95% CI, 48.8%-71.4%] to 65.2% [95% CI, 57.4%-72.3%]; P = .001) but decreased among children aged 6 to 10 years (from 64.6% [95% CI, 57.7%-70.9%] to 46.5% [95% CI, 39.1%-54.0%]; P < .001), adolescents aged 11 to 13 years (from 68.8% [95% CI, 58.1%-77.8%] to 26.2% [95% CI, 18.6%-35.5%]; P < .001), and adolescents aged 14 to 18 years (from 68.5% [95% CI, 62.9%-73.6%] to 15.6% [95% CI, 12.2%-19.8%]; P < .001). By birth year, serologic evidence of vaccine-associated immunity significantly decreased in the 1994-2003 NHANES birth cohort but not among those born between 1988 and 1993. Non-US-born children and adolescents did not show the same decreasing trend in immunity. Conclusions and Relevance: In this cross-sectional study, decreasing hepatitis B immunity was observed among US-born children and adolescents in the 1994-2003 NHANES birth cohort despite increasing rates of hepatitis B vaccination coverage. These findings suggest a possible need for surveillance and a booster vaccine dose for hepatitis B as those without serologic evidence of immunity become young adults and may engage in behaviors associated with an increased risk for infection.

Trends in CD4 and viral load testing 2005 to 2018: multi-cohort study of people living with HIV in Southern Africa.

INTRODUCTION: The World Health Organization (WHO) recommends a CD4 cell count before starting antiretroviral therapy (ART) to detect advanced HIV disease, and routine viral load (VL) testing following ART initiation to detect treatment failure. Donor support for CD4 testing has declined to prioritize access to VL monitoring. We examined trends in CD4 and VL testing among adults (≥15 years of age) starting ART in Southern Africa. METHODS: We analysed data from 14 HIV treatment programmes in Lesotho, Malawi, Mozambique, South Africa, Zambia and Zimbabwe in 2005 to 2018. We examined the frequency of CD4 and VL testing, the percentage of adults with CD4 or VL tests, and among those having a test, the percentage starting ART with advanced HIV disease (CD4 count <200 cells/mm3 ) or failing to suppress viral replication (>1000 HIV-RNA copies/mL) after ART initiation. We used mixed effect logistic regression to assess time trends adjusted for age and sex. RESULTS: Among 502,456 adults, the percentage with CD4 testing at ART initiation decreased from a high of 78.1% in 2008 to a low of 38.0% in 2017; the probability declined by 14% each year (odds ratio (OR) 0.86; 95% CI 0.86 to 0.86). Frequency of CD4 testing also declined. The percentage starting ART with advanced HIV disease declined from 83.3% in 2005 to 23.5% in 2018; each year the probability declined by 20% (OR 0.80; 95% CI 0.80 to 0.81). VL testing after starting ART varied; 61.0% of adults in South Africa and 10.7% in Malawi were tested, but fewer than 2% were tested in the other four countries. The probability of VL testing after ART start increased only modestly each year (OR 1.06; 95% CI 1.05 to 1.06). The percentage with unsuppressed VL was 8.6%. There was no evidence of a decrease in unsuppressed VL over time (OR 1.00; 95% CI 0.99 to 1.01). CONCLUSIONS: CD4 cell counting declined over time, including testing at the start of ART, despite the fact that many patients still initiated ART with advanced HIV disease. Without CD4 testing and expanded VL testing many patients with advanced HIV disease and treatment failure may go undetected, threatening the effectiveness of ART in sub-Saharan Africa.

[Seronegative antiphospholipid syndrome: Myth or reality?] / Syndrome des antiphospholipides « séronégatif ¼ : mythe ou réalité ?

The antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by thrombosis and/or obstetrical manifestations and the persistent presence, at least 12 weeks apart, of antiphospholipid antibodies (aPL) such as lupus anticoagulant (LA) and/or anticardiolipin antibodies (ACL) and/or anti-ß2 glycoprotein I antibodies (aß2GPI). The finding of patients with clinical profile highly suggestive of APS but who are negative for conventional biological criteria has led to the concept of seronegative APS. In the last few years, new antigen targets and methodological approaches have been employed to more clearly identify this syndrome in patients with thrombosis or obstetrical complications without conventional aPL. Although seronegative APS is still controversial, there is increasing recognition of the existence of this subgroup. However, clinical relevance of non conventional aPL need to be confirmed by efforts toward standardizing new biological tools and longitudinal studies involving large cohort of patients.

Progress in the serology-based diagnosis and management of adult celiac disease.

Introduction: This article provides a comprehensive overview of the development and application of serological tests used routinely in clinical practice for the diagnosis and management of adult celiac disease.Areas covered: We summarize existing scientific literature related to anti-endomyseal, anti-tissue transglutaminase, and anti-deamidated gliadin peptide antibodies and detail the current and potential future applications of these tests in celiac disease.Expert commentary: Current serological tests in celiac disease have some of the best performance characteristics among disease-specific tests. However, in adult celiac disease, current diagnostic algorithms still rely on duodenal biopsies to confirm the diagnosis. A 'biopsy avoidance strategy' has been implemented in pediatric celiac disease. Future high-quality studies will help inform on whether this approach can be implemented into adult gastroenterology services. It is envisaged that the next 5 years will see an increasing reliance on serology in the diagnosis of adult celiac disease.

Use and utility of serologic tests for rheumatoid arthritis in primary care.

INTRODUCTION: In this retrospective, register-based population study, we evaluated if anti-citrullinated protein antibodies (ACPA) is a better choice than immunoglobulin M rheumatoid factor (IgM RF) in primary care when rheumatoid arthritis (RA) is suspected, as it determines predictive values in real-life settings. Furthermore, the study described ordering patterns to investigate the benefit of repeated testing. METHODS: Test result, requisitioning unit, test date and the patient's social security number were collected from the Department of Clinical Immunology at Odense University Hospital in 2007-2016 and merged with patient diagnoses from the Danish National Patient Registry. RESULTS: Overall, 5% were diagnosed with RA. IgM RF remained the preferred test during the entire period. Test sensitivity was 61% for IgM RF and 54% for ACPA. The test specificity was 88% for IgM RF and 96% for ACPA. Positive predictive value (PPV) was higher for ACPA than for IgM RF (30% versus 12%) and negative predictive value (NPV) was equal (99%) in primary care. Few individuals seroconverted from negative to positive (ACPA 2% and IgM RF 5%) and positive to negative (ACPA 3% and IgM RF 6%). CONCLUSIONS: ACPA has a higher PPV for RA than IgM RF, whereas their NPV is identical. ACPA is the better choice when testing for RA in primary care. Seroconversion is rare, and it is only rarely relevant to retest. FUNDING: The Department of Clinical immunology at Odense University Hospital funded the study. TRIAL REGISTRATION: not relevant.

Tracking the uptake of outcomes of hepatitis B virus testing using laboratory data in Victoria, 2011-16: a population-level cohort study.

Background A priority area in the 2016 Victorian Hepatitis B Strategy is to increase diagnostic testing. This study describes hepatitis B testing and positivity trends in Victoria between 2011 and 2016 using data from a national laboratory sentinel surveillance system. METHODS: Line-listed diagnostic and monitoring hepatitis B testing data among Victorian individuals were collated from six laboratories participating in the Australian Collaboration for Coordinated Enhanced Sentinel Surveillance (ACCESS) of sexually transmissible infections and blood-borne viruses. Diagnostic tests included hepatitis B surface antigen (HBsAg)-only tests and guideline-based hepatitis B tests (defined as a single test event for HBsAg, hepatitis B surface antibody and hepatitis B core antibody). Using available data, the outcomes of testing and/or infection were further classified. Measures reported include the total number of HBsAg and guideline-based tests conducted and the proportion positive, classified as either HBsAg positive or chronic hepatitis B infection. RESULTS: The number of HBsAg tests decreased slightly each year between 2011 and 2016 (from 91043 in 2011 to 79664 in 2016; P < 0.001), whereas the number of guideline-based hepatitis B tests increased (from 8732 in 2011 to 16085 in 2016; P <0.001). The proportion of individuals classified as having chronic infection decreased from 25% in 2011 to 7% in 2016, whereas the proportion classified as susceptible and immune due to vaccination increased (from 29% to 39%, and from 27% to 34%, respectively; P < 0.001). CONCLUSIONS: The study findings indicate an increased uptake of guideline-based hepatitis B testing. The ongoing collection of testing data can help monitor progress towards implementation of the Victorian Hepatitis B Strategy.

Serology in the xxi century: is it still of interest? / Serología en el siglo xxi: ¿continúa teniendo interés?

Serological techniques have developed in recent years, and are now more sensitive, automated and easier to interpret. However, serology in often being replaced by direct diagnosis based on molecular biology, essentially PCR (polymerase chain reaction) techniques. Nevertheless, in some cases, serology continues to be an essential feature in the routine work of microbiology laboratories, such as in screening pregnant wo-men, studies of transplant donors and recipients, diagnosis of certain viruses and bacteria, and epidemiological and prevalence studies. The improved speed, sensitivity and specificity of direct diagnostic methods will probably continue to decrease antibody-based diagnosis. Thus, serology will not be relevant in the management of acute patient infections; however, it will continue to be relevant in population-based studies and in certain syndromic studies, with more automated and more sensitive, specific and cheap methods. Supplement information: This article is part of a supplement entitled «SEIMC External Quality Control Programme. Year 2016¼, which is sponsored by Roche, Vircell Microbiologists, Abbott Molecular and Francisco Soria Melguizo, S.A. © 2019 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosasy Microbiología Clínica. All rights reserved.

Immunoglobulins and virus antibody titers: of past needs, current requirements, and future options.

BACKGROUND: Immunoglobulins (Igs) have been in clinical use for almost 70 years, and early on were also used in conjunction with exposure to the measles virus or polio virus. The US regulations that describe functional Ig lot release thus require the demonstration of minimum antibody titers against these two viruses, although the use of vaccines has now dramatically reduced their incidence. The lower clinical importance of these viruses raises the question of whether other virus antibodies might be more informative for patients with immunodeficiency. STUDY DESIGN AND METHODS: A literature survey was conducted to identify viruses of potential clinical concern for people with immunodeficiency. The viruses selected have stable seroepidemiology and associated functional antibody assays. As a result, neutralizing antibody titers to human adenovirus 5 (HAdV5), respiratory syncytial virus (RSV) serotypes A and B, and human parainfluenza virus 3 (hPIV3) were determined in Ig lots produced from plasma collected in either the United States or the European Union. RESULTS: The virus antibody titers measured were high and consistent among the Ig lots tested. Use of either US- or EU-derived plasma as starting material resulted in equivalent virus antibody titers, with the exception of RSV serotype B, for which a lower titer was seen in EU plasma-derived Ig lots. CONCLUSION: With the significant decline in measles virus and polio virus circulation, and even their potential eradication, measurement of antibody titers against other viruses in Ig products may be more informative for functional lot release testing.

Rheumatologic Tests: A Primer for Family Physicians.

Patients with a suspected connective tissue disorder should undergo serologic testing to confirm the diagnosis and, in some cases, to monitor disease activity and predict flares. Patients with suspected systemic lupus erythematosus should be tested for antinuclear antibodies. However, antinuclear antibodies are not specific and may be present in many other connective tissue disorders and nonrheumatologic diseases. Thus, patients with suspected systemic lupus erythematosus should undergo further testing to confirm the diagnosis. Patients with Sjögren syndrome may have a positive antinuclear antibody titer, but often also have positive anti-Sjögren antigen A or B results. Similarly, antinuclear antibodies can be present in patients with scleroderma, mixed connective tissue disease, and dermatomyositis or polymyositis. Additional tests are needed to help confirm the diagnosis. In patients with findings of rheumatoid arthritis, a positive rheumatoid factor titer suggests the diagnosis, but as with antinuclear antibodies, it is not specific and can occur in other conditions. Rheumatoid factor can also be negative in patients with rheumatoid arthritis. A positive anticyclic citrullinated peptide antibody titer is more specific for rheumatoid arthritis and can help confirm the diagnosis. Physicians should order these serologic tests only when patients have a high pretest probability of a specific connective tissue disorder.

Practice Pattern of Hepatitis B Testing in Rheumatoid Arthritis Patients: A Cross-National Comparison Between the US and Taiwan.

OBJECTIVE: The hepatitis B virus (HBV) testing rates and patterns in rheumatoid arthritis (RA) patients starting disease-modifying antirheumatic drugs (DMARDs) have not been well studied. We describe and compare the practice patterns of HBV testing among RA patients in the US and Taiwan. METHODS: We conducted a retrospective cohort study, including RA patients starting a first DMARD in the US or Taiwan. The first date patients newly received any DMARD was defined as the index date, and the 1-year period before the index date was the baseline period. HBV testing was defined as any of the following tests 1 year before or after the index date: hepatitis B surface antigen, hepatitis B surface antibody, hepatitis B core antibody, hepatitis B envelope antigen, hepatitis B envelope antibody, or HBV DNA. We calculated the HBV testing rate by year and used Poisson regression to calculate the testing rate ratio. RESULTS: We identified 14,568 RA patients in the US and 46,265 in Taiwan. The overall testing rate was 20.3% in the US and 24.5% in Taiwan, and gradually increased over the study period from 13.1-23.0% in the US and 16.8-30.0% in Taiwan. More than one type of HBV test was used in 43.4% of patients in the US and 16.3% of patients in Taiwan receiving tests. Results of Poisson regression found Taiwan had a 17% higher testing rate over the US during the followup period (crude rate ratio 1.17 [95% confidence interval 1.12-1.22]). CONCLUSION: We found small differences in the HBV testing rates across the US and Taiwan. Although the rate gradually increased in the past decade, it remained low in both countries.

Advances in Serodiagnostic Testing for Lyme Disease Are at Hand.

The cause of Lyme disease, Borrelia burgdorferi, was discovered in 1983. A 2-tiered testing protocol was established for serodiagnosis in 1994, involving an enzyme immunoassay (EIA) or indirect fluorescence antibody, followed (if reactive) by immunoglobulin M and immunoglobulin G Western immunoblots. These assays were prepared from whole-cell cultured B. burgdorferi, lacking key in vivo expressed antigens and expressing antigens that can bind non-Borrelia antibodies. Additional drawbacks, particular to the Western immunoblot component, include low sensitivity in early infection, technical complexity, and subjective interpretation when scored by visual examination. Nevertheless, 2-tiered testing with immunoblotting remains the benchmark for evaluation of new methods or approaches. Next-generation serologic assays, prepared with recombinant proteins or synthetic peptides, and alternative testing protocols, can now overcome or circumvent many of these past drawbacks. This article describes next-generation serodiagnostic testing for Lyme disease, focusing on methods that are currently available or near-at-hand.

Development of Zika Virus Serological Testing Strategies in New York State.

The recent outbreak of Zika virus (ZIKV) in the Americas has challenged diagnostic laboratory testing strategies. At the Wadsworth Center, ZIKV serological testing was performed for over 10,000 specimens, using a combination of an enzyme-linked immunosorbent assay (ELISA) for IgM antibodies (Abs) to ZIKV, a polyvalent microsphere immunoassay (MIA) to detect Abs broadly reactive with flaviviruses, and a plaque reduction neutralization test (PRNT) for further testing. Overall, 42% of patients showed serological evidence of flavivirus infection (primarily past dengue virus [DENV] infection), while 7% possessed IgM Abs to ZIKV and/or DENV. ZIKV IgM Abs typically arose within 3 to 4 days, with only one instance of duration beyond 100 days after reported symptoms. PRNT analysis of 826 IgM-positive specimens showed 7% positive neutralization to ZIKV alone, 9% to DENV alone, and 85% to both ZIKV and DENV. Thus, the extensive Ab cross-reactivity among flaviviruses significantly reduced the value of performing PRNT analysis, especially when a traditional paired serum algorithm with viral neutralization titering was used. Nevertheless, the finding of a negative ZIKV result by PRNT was invaluable for reassuring both physicians and patients. The MIA detected both IgM and IgG, which enabled us to identify patients who presented without IgM anti-ZIKV Abs but still had ZIKV-specific neutralizing Abs. On the basis of these results, a new algorithm, which included an IgM Ab capture (MAC)-ELISA to detect recent infection, a flavivirus MIA to identify patients no longer producing IgM, and a single-dilution PRNT for ZIKV exclusion and occasional discrimination of ZIKV and DENV, was implemented.

HIV Testing Among "MSM": Prevention Technologies, Sexual Moralities and Serologic Self-surveillance / A testagem do HIV entre "HSH": tecnologias de prevenção, moralidade sexual e autovigilância sorológica

Abstract Global AIDS guidelines have prioritized the expansion of HIV testing among the groups most exposed to the virus, such as those referred to as men who have sex with men (MSM). This paper analyses the relationships between the production of prevention strategies and sexual moralities based on the results of a systematic review of academic literature about testing with gays and MSM (2005-2015, using the PubMed, Sociological Abstract and Lilacs databases). The analysis of 65 articles reveals the recruitment strategies for identifying target-subjects and how they are held responsible for their serological self-surveillance, including routine tests. The findings also point to a diversification of testing locations. Implicit assumptions about sexuality and gay affection are conveyed through the interventions' emphasis on sociability spaces and occasional sex, especially when facilitated by the use of apps. Attentive to the symbolic dimensions of the new prevention technologies and strategies, we argue that the expansion of testing with a focus on "MSM" signals a displacement of health interventions. If before actions to control the epidemic sought to intervene in sexual practices, the current efforts are concentrated on promoting self-surveillance of one's serological status.

Resumo As diretrizes globais de prevenção da Aids têm priorizado a ampliação da testagem do HIV entre grupos mais expostos ao vírus, como os denominados homens que fazem sexo com homens (HSH). Com base em revisão sistemática da produção acadêmica (2005-2015) nas bases PubMed, Sociological Abstract e Lilacs, sobre testagem com gays e HSH e formas de captação para diagnóstico, este trabalho analisa as relações entre produção de estratégias de prevenção e moralidades sexuais. O exame dos 65 artigos revela os modos de identificação dos sujeitos-alvo das estratégias de captação e de responsabilização pela própria vigilância sorológica, incluindo a testagem de rotina. Os achados apontam ainda a diversificação de lugares para testagem. Os pressupostos implícitos sobre sexualidade e afetividade gay se exprimem através da ênfase das intervenções nos espaços de sociabilidade e de sexo ocasional, particularmente quando facilitado pelo uso de aplicativos. Atentos à dimensão simbólica das novas estratégias e tecnologias de prevenção, argumentamos que a ampliação da testagem com foco nos "HSH" opera um deslocamento da intervenção sanitária. Se antes as medidas de controle da epidemia visavam intervir no exercício da sexualidade dos sujeitos, os esforços atuais se concentram em promover a autovigilância do estado sorológico.

Clinical and serological characteristics of nail psoriasis in Indian patients: A cross-sectional study.

BACKGROUND: Nail involvement in psoriasis is common with a lifetime incidence of 80-90%. It may reflect severity of cutaneous involvement and predict joint disease. Yet it remains, poorly studied and evaluated especially in Indian psoriatic patients. AIM: The present study was undertaken to evaluate clinical and serological profile of nail involvement in psoriasis and to assess quality of life impairment associated with nail involvement in Indian patients. METHODS: Consecutive patients with nail psoriasis were assessed for severity of cutaneous disease (psoriasis area severity index score) and nail disease (nail psoriasis severity index score). The impairment in quality of life attributable to nail disease was scored with nail psoriasis quality of life 10 score. All patients were also assessed for joint disease and tested for inflammatory and serological markers as erythrocyte sedimentation rate, C-reactive protein, rheumatoid factor and anti-cyclic citrullinated peptide antibodies. RESULTS: In our cohort of 38 patients with nail psoriasis, 9 had concomitant psoriatic arthritis. The mean psoriasis area severity index was 14.4 ± 9.6 (range = 0.4-34). The most commonly recorded psoriatic nail changes were pitting (97.4%), onycholysis (94.7%) and subungual hyperkeratosis (89.5%). The mean nail psoriasis severity index score was 83.2 ± 40.1 (range = 5-156) and mean nail psoriasis quality of life 10 was 1.1 ± 0.4. Erythrocyte sedimentation rate and C-reactive protein were raised in 22/38 (57.9%) and 15/38 (39.5%) patients, respectively; rheumatoid factor was positive in 5/38 (13.2%) and anti-cyclic citrullinated peptide antibody was raised in 4/38 (10.5%) patients. LIMITATIONS: Small sample size and lack of a control group. CONCLUSIONS: In Indian patients with nail psoriasis, severity of nail involvement was found to be poorly correlated with the extent of cutaneous disease. In addition the impact of nail disease on patient's quality of life was found to be minimal. This suggests the need for a quality of life questionnaire suited to the Indian population. Serological markers were raised overall in the study patients and more so in the patients with concomitant arthritis.

Relevance of and New Developments in Serology for Toxoplasmosis.

Toxoplasmosis is a widespread parasitic disease caused by the intracellular parasite Toxoplasma gondii with a wide spectrum of clinical outcomes. The biological diagnosis of toxoplasmosis is often difficult and of paramount importance because clinical features are not sufficient to discriminate between toxoplasmosis and other illnesses. Serological tests are the most widely used biological tools for the diagnosis of toxoplasmosis worldwide. This review focuses on the crucial role of serology in providing answers to the most important questions related to the epidemiology and diagnosis of toxoplasmosis in human pathology. Notwithstanding their undeniable importance, serological tools need to be continuously improved and the interpretation of the ensuing results remains complex in many circumstances.

Diagnosis of Lyme disease in the pediatric acute care setting.

PURPOSE OF REVIEW: We review the current evidence concerning the diagnosis of Lyme disease in children for application in the acute care setting. RECENT FINDINGS: Recent studies suggest that Lyme disease incidence is substantially higher than previously described. Although efforts are ongoing to identify alternative testing strategies, two-tiered serologic testing remains the diagnostic standard in children with compatible clinical syndromes. Published clinical prediction rules can assist clinicians caring for children with potential Lyme disease. SUMMARY: Two-tiered serologic testing remains the mainstay of the diagnosis of Lyme disease. To minimize the risk of a false positive test, serologic testing should be limited to those children with symptoms compatible with Lyme disease with potential exposure to ticks from endemic regions.

The Past, Present, and (Possible) Future of Serologic Testing for Lyme Disease.

Lyme disease prevails as the most commonly transmitted tick-borne infection in the United States, and serologic evaluation for antibodies to Borrelia burgdorferi remains the recommended modality for diagnosis. This review presents a brief historical perspective on the evolution of serologic assays for Lyme disease and provides a summary of the performance characteristics for the currently recommended two-tiered testing algorithm (TTTA). Additionally, a recently proposed alternative to the traditional TTTA is discussed, and novel methodologies, including immuno-PCR and metabolic profiling for Lyme disease, are outlined.

Contemporary celiac disease diagnosis: is a biopsy avoidable?

PURPOSE OF REVIEW: The duodenal biopsy is the gold standard for the diagnosis of celiac disease. However, given improvements in the performance of serological testing, the possibility of accurately diagnosing celiac disease without the need of a biopsy has attracted interest. The European Society for Paediatric Gastroenterology, Hepatology and Nutrition has revised its recommendations to include a diagnostic algorithm that includes sequential serological testing and human leukocyte antigen genotyping for symptomatic children which would enable a diagnosis of celiac disease to be made in the absence of a confirmatory intestinal biopsy. RECENT FINDINGS: Recent studies have evaluated the ESPGHAN guidelines and have mostly corroborated that celiac disease can be accurately diagnosed in specific pediatric patient populations without the need of a biopsy. However, two cautionary points have been raised that warrant further consideration - the success of this approach is highly dependent targeting a population with a high pretest probability of celiac disease, as well, the performance of serology assays must be established and the appropriate use of cutoffs is essential. SUMMARY: The duodenal biopsy will remain the gold standard for diagnosing celiac disease in a majority of patients. However, as serology assays evolve and as a greater understanding of the genetic risk factors of celiac disease is achieved, more patients may be accurately diagnosed without the need for a biopsy.