Utility of serological markers in inflammatory bowel diseases: Gadget or magic?

The panel of serologic markers for inflammatory bowel diseases (IBD) is rapidly expanding. Although anti-Saccharomyces cerevisiae antibodies (ASCA) and atypical perinuclear antineutrophil cytoplasmic antibodies (P-ANCA) remain the most widely investigated, an increasing amount of experimental data is available on newly discovered antibodies directed against various microbial antigens. The role of the assessment of various antibodies in the current IBD diagnostic algorithm is often questionable due to their limited sensitivity. In contrast, the association of serologic markers with disease behavior and phenotype is becoming increasingly well-established. An increasing number of observations confirms that patients with Crohn's disease expressing multiple serologic markers at high titers are more likely to have complicated small bowel disease (e.g. stricture and/or perforation) and are at higher risk for surgery than those without, or with low titers of antibodies. Creating homogenous disease sub-groups based on serologic response may help develop more standardized therapeutic approaches and may help in a better understanding of the pathomechanism of IBD. Further prospective clinical studies are needed to establish the clinical role of serologic tests in IBD

Diagnostic Accuracy of Five Serologic Tests for Strongyloides stercoralis Infection

Background:The diagnosis of Strongyloides stercoralis (S. stercoralis) infection is hampered by the suboptimal sensitivity of fecal-based tests. Serological methods are believed to be more sensitive, although assessing their accuracy is difficult because of the lack of sensitivity of a fecal-based reference ("gold") standard.Methods:The sensitivity and specificity of 5 serologic tests for S. stercoralis (in-house IFAT, NIE-ELISA and NIE-LIPS and the commercially available Bordier-ELISA and IVD-ELISA) were assessed on 399 cryopreserved serum samples. Accuracy was measured using fecal results as the primary reference standard, but also using a composite reference standard (based on a combination of tests).Results:According to the latter standard, the most sensitive test was IFAT, with 94.6% sensitivity (91.2-96.9), followed by IVD-ELISA (92.3%, 87.7-96.9). The most specific test was NIE-LIPS, with specificity 99.6% (98.9-100), followed by IVD-ELISA (97.4%, 95.5-99.3). NIE-LIPS did not cross-react with any of the specimens from subjects with other parasitic infections. NIE-LIPS and the two commercial ELISAs approach 100% specificity at a cut off level that maintains ≥70% sensitivity.Conclusions:NIE-LIPS is the most accurate serologic test for the diagnosis of S. stercoralis infection. IFAT and each of the ELISA tests are sufficiently accurate, above a given cut off, for diagnosis, prevalence studies and inclusion in clinical trials.Fil: Bisoffi, Zeno. Sacro Cuore Hospital; ItaliaFil: Buonfrate, Dora. Sacro Cuore Hospital; ItaliaFil: Sequi, Marco. Istituto Di Ricerche Farmacologiche Mario Negri; ItaliaFil: Mejia, Rojelio. National Institute Of Allergy And Infectious Diseases; Estados UnidosFil: Cimino, Rubén Oscar. Universidad Nacional de Salta. Sede Regional Orán. Instituto de Investigación de Enfermedades Tropicales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Krolewiecki, Alejandro Javier. Universidad Nacional de Salta. Sede Regional Orán. Instituto de Investigación de Enfermedades Tropicales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Albonico, Marco. Sacro Cuore Hospital; ItaliaFil: Gobbo, Maria. Sacro Cuore Hospital; ItaliaFil: Bonafini, Stefania. Sacro Cuore Hospital; ItaliaFil: Angheben, Andrea. Sacro Cuore Hospital; ItaliaFil: Requena-Mendez, Ana. Universidad de Barcelona; EspañaFil: Muñoz, José. Universidad de Barcelona; EspañaFil: Nutman, Thomas B.. National Institute Of Allergy And Infectious Diseases; Estados Unido

In-House RT-PCR Assay for Detection of Human Immunodeficiency Virus Type 1 Infection

Serologic assays are commonly used for screening (ELISA) and for confirmation (Western blot) of HIV-1 infection; however, both assays have potentially yielded the false-positive or false-negative results. In this study, a diagnostic RT-PCR assay as an alternative test for detection of HIV-1 was developed. Forty-six plasma specimens from highly risky groups, who visited a voluntary counseling and testing for HIV (VCT) in Sanglah Clinic of General Hospital, Denpasar, Bali, were tested by RT-PCR assay with specific primers for Pol region of HIV-1 genome. The results of the RT-PCR tests were then compared with those of serologic tests to obtain the sensitivity and specificity of RT-PCR assay. The results of this study showed that the RT-PCR assay could detect 17 (sensitivity: 65.4%) of 26 serologically positive specimens and was unexpectedly able to detect 2 (specificity: 90%) of 20 serologically negative specimens. Thus, the RT-PCR assay developed in this study is potential to be used as an alternative test, even though there are numerous aspects, particularly the sensitivity, that need to be improved in further research

Coccidioidomycosis Complement Fixation Titer Trends in the Age of Antifungals.

Coccidioidomycosis is associated with a broad spectrum of illness severity, ranging from asymptomatic or self-limited pulmonary infection to life-threatening manifestations of disseminated disease. Serologic studies before the widespread availability of antifungals established current understanding of serologic kinetics and dynamics. Chart histories and complement fixation (CF) titer trends were analyzed for 434 antifungal-treated coccidioidomycosis patients, who were classified by three infectious disease physicians as having either pulmonary uncomplicated coccidioidomycosis (PUC) (n = 248), pulmonary chronic coccidioidomycosis (PCC) (n = 64), disseminated coccidioidomycosis (DC) not including meningitis (n = 86), or coccidioidal meningitis (CM) (n = 36). The median maximal CF titers were 1:4 for PUC patients, 1:24 for PCC patients, 1:128 for DC patients, and 1:32 for CM patients. Approximately 25.4% of PUC patients, 6.2% of PCC patients, 2.3% of DC patients, and 8.3% of CM patients did not develop detectable titers during the study period. Maximal titers developed a mean of 31 days (95% confidence interval [CI], 13 to 50 days) after initial serologic positivity, with no significant differences between groups. Serologic recurrence occurred in 9% of PUC patients, 36% of PCC patients, 50% of DC patients, and 52% of CM patients. Median titer improvement rates were 91 days/dilution for PUC patients, 112 days/dilution for PCC patients, 136 days/dilution for DC patients, and 146 days/dilution for CM patients. Receiver operating characteristic (ROC) analysis revealed that CF testing retains moderate classification value for disseminated infections (area under the curve [AUC], 0.82 [95% CI, 0.78 to 0.87]) and complicated infections (AUC, 0.82 [95% CI, 0.77 to 0.86]). A suitable cutoff value for complicated infections is ≥1:32. Findings update serologic parameters that are relevant for clinical assessment of coccidioidomycosis patients in the triazole era

Impact of antiretroviral therapy on adult HIV prevalence in a low-income rural setting in Uganda: a longitudinal population-based study.

OBJECTIVE: To estimate the contribution to HIV prevalence of lives saved due to the introduction of antiretroviral therapy (ART) in rural Uganda in 2004. DESIGN: Open population-based cohort study. METHODS: An open general population cohort with annual demographic and HIV serostatus data is used to estimate annual HIV prevalence, HIV incidence, and mortality from 2000 to 2010. We calculated standardized mortality rates among HIV-positive adults and the expected number of deaths in the cohort if ART had not been available during 2004-2010, based on the average mortality rate in the 4 years (2000-2003) before ART introduction. RESULTS: During 2004-2010, the estimated prevalence increased by 29% from 6.9% to 8.9%. HIV incidence was 5.6 cases per 1000 person-years in 2004, falling to 3.9 cases per 1000 person-years in 2006, and slightly rising to 5.1 in 2010. There was an increase of 182 in the number of HIV-positive participants during that period, cumulatively 228 lives were saved due to ART. Expected lives saved due to ART accounted for an increasing proportion of the estimated HIV prevalence from 4.0% in 2004 to 29.4% in 2010. CONCLUSIONS: Expected lives saved due to ART largely accounted for the increased estimated HIV prevalence from 2004 to 2010. Because HIV prevalence survey results are important for planning, programming, and policy, their interpretation requires consideration of the increasing impact of ART in decreasing mortality

Possible role of TORCH agents in congenital malformations in Gorgan, northern Islamic Republic of Iran

This descriptive, cross-sectional study was carried out to explore the frequency of contamination with TORCH agents in neonates with congenital malformations in a referral centre in Gorgan city, Islamic Republic of Iran. Blood samples were taken from 64 neonates and their mothers over a 20-month period in 2003-04. Serologic tests showed that 4/64 infants born with congenital malformations (6%) had positive IgM antibody titres for Toxoplasma gondii (2 cases), rubella virus (1 case) and cytomegalovirus (1 case). IgM was positive in 9/63 mothers (14%), also for T. gondii (3 cases), rubella virus (3 cases) and cytomegalovirus (3 cases). No cases of herpes simplex virus type II or Treponema pallidum were found

EPI Update, July 6, 2007

Weekly newsletter for Center For Acute Disease Epidemiology of Iowa Department of Public Health

Integrated Serologic Surveillance of Population Immunity and Disease Transmission.

Antibodies are unique among biomarkers in their ability to identify persons with protective immunity to vaccine-preventable diseases and to measure past exposure to diverse pathogens. Most infectious disease surveillance maintains a single-disease focus, but broader testing of existing serologic surveys with multiplex antibody assays would create new opportunities for integrated surveillance. In this perspective, we highlight multiple areas for potential synergy where integrated surveillance could add more value to public health efforts than the current trend of independent disease monitoring through vertical programs. We describe innovations in laboratory and data science that should accelerate integration and identify remaining challenges with respect to specimen collection, testing, and analysis. Throughout, we illustrate how information generated through integrated surveillance platforms can create new opportunities to more quickly and precisely identify global health program gaps that range from undervaccination to emerging pathogens to multilayered health disparities that span diverse communicable diseases

Variation in HIV-1 set-point viral load: epidemiological analysis and an evolutionary hypothesis.

The natural course of HIV-1 infection is characterized by a high degree of heterogeneity in viral load, not just within patients over time, but also between patients, especially during the asymptomatic stage of infection. Asymptomatic, or set-point, viral load has been shown to correlate with both decreased time to AIDS and increased infectiousness. The aim of this study is to characterize the epidemiological impact of heterogeneity in set-point viral load. By analyzing two cohorts of untreated patients, we quantify the relationships between both viral load and infectiousness and the duration of the asymptomatic infectious period. We find that, because both the duration of infection and infectiousness determine the opportunities for the virus to be transmitted, this suggests a trade-off between these contributions to the overall transmission potential. Some public health implications of variation in set-point viral load are discussed. We observe that set-point viral loads are clustered around those that maximize the transmission potential, and this leads us to hypothesize that HIV-1 could have evolved to optimize its transmissibility, a form of adaptation to the human host population. We discuss how this evolutionary hypothesis can be tested, review the evidence available to date, and highlight directions for future research