False-positive Serology Research Articles

No detection of tick-borne encephalitis virus RNA in blood, urine or saliva of hospitalised immunocompetent tick-borne encephalitis patients.

Tick-borne encephalitis (TBE) is usually diagnosed based on the presence of TBE virus (TBEV)-specific IgM and IgG antibodies in serum. However, antibodies induced by vaccination or cross-reactivity to previous flavivirus infections may result in false positive TBEV serology. Detection of TBEV RNA may be an alternative diagnostic approach to detect viral presence and circumvent the diagnostic difficulties present when using serology. Viral RNA in blood is commonly detectable only in the first viremic phase usually lasting up to two weeks, and not in the second neurologic phase, when the patients contact the health care system and undergo diagnostic work-up. TBEV RNA has previously been detected in urine in a few retrospective TBE cases in the neurologic phase, and furthermore RNA of other flaviviruses has been detected in patient saliva. In this study, blood, saliva and urine were collected from 31 hospitalised immunocompetent patients with pleocytosis and symptoms of aseptic meningitis and/or encephalitis, suspected to have TBE. We wanted to pursue if molecular testing of TBEV RNA in these patient materials may be useful in the diagnostics. Eleven of the 31 study patients were diagnosed with TBE based on ELISA detection of TBEV specific IgG and IgM antibodies. None of the study patients had TBEV RNA detectable in any of the collected patient material.

CHRONIC GASTRITIS IN PEDIATRIC PATIENTS; HELICOBACTER PYLORI OR CELIAC DISEASE?

Objective: We aimed to determine the frequency of Celiac disease (CD) and Helicobacter pylori (Hp) infection, and the effect of Hp and chronic gastritis on patients with false positive CD serology in our center. Material and Methods: We included 194 patients who had both stomach and small intestine biopsies and were diagnosed with chronic gastritis, between January 2021 and December 2022 in the study. Patients were divided into two groups: Hp- positive and Hp-negative. Additionally, we evaluated the frequency and association of Hp in cases who were serologically suspected with CD but whose biopsies were not compatible with celiac disease histopathologically. Results: Helicobacter pylori infection was detected in 76 of 194 gastric biopsies examined (39.1%). Hp positivity was detected in only 15 of 27 patients (55.5%) diagnosed with CD and CD serology was positive in 39 of 194 patients (20.1%), but histopathological changes compatible with CD were detected in only 27 (13.9%). Conclusion: Although the relationship between chronic gastritis and Hp is clear, the relationship between Hp and CD remains unclear. We believe that studies with larger patient groups investigating Hp virulence and its effect on CD pathophysiology are needed to reveal this relationship.

Autoantibody profiles in intravenous immunoglobulin preparations: A possible cause of mistaken autoimmunity diagnosis.

Intravenous immunoglobulins (IVIgs) derived from the pooled plasma of thousands of donors contain numerous types of IgG molecules, including autoantibodies commonly used to diagnose autoimmunity. While these autoantibodies can cause misinterpretation of serological tests for IVIg recipients, their profiles in IVIg preparations are not fully understood. Using binding-capability based immune assays, we measured 18 varieties of clinically relevant autoantibodies in domestic blood donor-derived IVIg products. In addition, we analyzed an IVIg product from a US brand to evaluate the influence of regional and racial differences. Based on the determined autoantibody titers, pharmacokinetics of passively acquired autoantibodies and their possible detection period in serum were estimated. Anti-thyroglobulin (Tg), anti-thyroidperoxidase (TPO), and anti-Sjögren's-syndrome-related antigen A (SS-A) antibodies were present in considerable amounts in IVIg products. Notably, these three autoantibodies can be detected in IVIg recipients' sera for up to 3 months after infusion. To the best of our knowledge, this is the first study that analyzed multiple autoantibody profiles in both pooled plasma and IVIg products and that further evaluated their potential influences on diagnosis of autoimmunity. Clinicians should keep in mind that IVIgs contain several autoantibodies and that their infusion can produce false-positive serology results. To establish an accurate diagnosis, serological tests must be carefully interpreted and clinical symptoms should be more purposefully considered if patients are receiving IVIg therapy.

Dengue COVID-19 overlap: antigenic mimicry or concurrent two viral diseases

Background: Dengue-COVID-19 overlap is mixture of both diseases sharing few similarities in pulmonary and extrapulmonary involvement. Due to high prevalence of both diseases later being pandemic disease, and overlapping laboratory and clinical parameters we have conducted a study to observe dengue-COVID-19 overlap in Indian settings in tertiary care hospitals.
 Methods: Prospective, observational study, included 600 COVID-19 cases with dengue NS1 or Dengue IgM positive, with lung involvement documented and categorized on HRCT thorax at entry point. All cases were subjected to dengue IgG antibody titers and dengue IgM/IgG antibody titer analysis after 12 weeks of discharge form hospital.
 Results: Dengue- COVID-19 overlap was documented in 16.33% (98/600) cases. CT severity has documented significant correlation with Dengue-COVID-19 overlap cases. [p<0.00001] Hematological evaluation, white blood cell count & platelet count were having significant association with Dengue-COVID-19 overlap [p<0.0076] & [p<0.00001] respectively. Clinical parameters as hypoxia have significant association with dengue- COVID-19 overlap. [p<0.00001] Inflammatory markers as IL-6, CRP and LDH has significant association in dengue-COVID-19overlap [p<0.00001] respectively. In study of 98 cases of ‘Dengue-COVID-19’, post covid lung fibrosis [p<0.004] and serological assessment in dengue IgM/IgG and covid antibody titers has significant association [p<0.00001]
 Conclusion: Dengue-COVID-19 overlap is clinical syndrome with overlapping clinical and laboratory workup of both the illnesses. High index of suspicion is must in all covid cases in tropical settings where dengue is endemic; and all cases with leucopenia and thrombocytopenia with fever should be screened for dengue serology. False positive dengue serology or dengue antigen crossreactivity is known to occur in underlying COVID-19 illness, and have impact on clinical outcome as it will result in delay in covid appropriate treatment initiation and many cases require intensive care unit treatment due to progressed covid pneumonia.
 Bangladesh Journal of Medical Science Vol. 23 No. 01 January’24 Page : 189-199

Giardia lamblia Diagnosed During Upper Gastrointestinal Endoscopy: Clinical Manifestation, Histopathologic Findings and the Association With Celiac Disease.

Giardia lamblia may be found incidentally during upper gastrointestinal (GI) endoscopy, including when biopsies are taken for celiac disease (CeD) diagnosis. We aimed to study the clinical presentation and histopathology of G. lamblia and determine its association with CeD. A retrospective case series of pediatric patients diagnosed with G. lamblia based on intestinal biopsies between January 1999 and January 2023. Baseline data; demographics, symptoms, celiac serology, stool testing, macroscopic and histopathologic findings. Follow-up data; treatment and repeated celiac serology. Of 38 patients with G. lamblia , 15 (39.5%) were female, mean age of 6.7 (±4.8 SD) years. Clinical symptoms; GI 19/38 (50%), growth retardation and/or iron deficiency anemia 8/38 (21.1%) or a combination 11/38 (28.9%). Celiac serology was positive in 13/38 (34.2%). Duodenal endoscopic findings; normal (n = 23, 60.5%), nodularity (n = 12, 32.4%), erosions in 2 (5.4%) and scalloping in 1 (2.7%). Histopathology; normal villi 24/38 (63.2%), villous shortening with increased intraepithelial lymphocytes (IEL) 5/38 (13.2%), isolated IEL 3/38 (7.9%) and duodenitis in 6/38 (15.8%). Children with positive CeD serology were younger (4 vs. 8.1 years, P = 0.019), had fewer GI symptoms (23.1% vs. 64%, P = 0.017) and a higher rate of villous shortening with increased IEL (38.5% vs. 0, P < 0.001) versus children with negative serology. On follow-up, metronidazole treatment was recommended to all but was documented to be given in 22/38 (57.9%). Among the 13 children with positive CeD serology, serology normalized in 10 (77%). G. lamblia is a rare histopathologic finding in children. It may be an incidental finding in CeD or may cause false positive celiac serology.

False-Positive Serology for Rocky Mountain Spotted Fever in Long Island, New York, during 2011–2021

Cases of rocky mountain spotted fever (RMSF) are increasingly reported every year in Long Island, New York. In clinical practice, an uncommonly high number of referrals with a positive RMSF IgG test result have been seen in our tick-borne disease clinic. The aim of this study is to describe the clinical-epidemiological characteristics and outcomes of hospitalized patients with positive serologies for RMSF in our academic center in Long Island, NY. We found that out of twenty-four patients with a positive serology for RMSF, only one case met the case definition per CDC criteria, two had suspected RMSF, and the other twenty-one did not have a clinical picture consistent with RMSF. A high number of false-positive RMSF serology may be due to other spotted fever rickettsioses in Long Island. Further studies are needed to investigate the presence of another Rickettsia spp. (such as Rickettsia amblyommatis) in this area that may affect humans.

Increased risk of false-positive HIV ELISA results after COVID-19.

From the first-generation options available in 1985, tests to detect HIV-1 specific antibodies have increased its sensitivity and specificity. HIV-1 and SARS-CoV-2 surface glycoproteins present a certain degree of homology and shared epitope motifs, which results of relevance as both pandemics coexist. Here, we aimed to evaluate the rate of false-positive HIV serology results among individuals with COVID-19 diagnosis and in vaccinated individuals. A retrospective analysis of the samples stored at the Infectious Disease Biobank in Argentina from donors with previous COVID-19 diagnosis or anti-SARS-CoV-2 vaccination. Plasma samples were analyzed using Genscreen Ultra HIV Ag-Ab. In those with a positive result, the following assays were also performed: ELISA lateral flow Determine Early Detect; RecomLine HIV-1 & HIV-2 IgG and Abbott m2000 RealTime PCR for HIV-1 viral load quantification. In all samples, the presence of anti-SARS-CoV-2 IgG antibodies was evaluated by ELISA using the COVIDAR kit. Statistical analysis was done using Pearson's and Fisher's exact chi-squared test; Mann-Whitney and Kruskal-Wallis tests. Globally, the false-positive HIV ELISA rate was 1.3% [95% confidence interval (95% CI) 0.66-2.22; χ2 = 4.68, P = 0.03, when compared with the expected 0.4% false-positive rate]. It increased to 1.4% (95% CI 0.70-2.24, χ2 = 5.16, P = 0.02) when only samples from individuals with previous COVID-19 diagnosis, and to 1.8% (95% CI 0.91-3.06, χ2 = 7.99, P = 0.005) when only individuals with detectable IgG SARS-CoV-2 antibodies were considered. This higher occurrence of HIV false-positive results among individuals with detectable antibodies against Spike SARS-CoV-2 protein should be dispersed among virology testing settings, health providers, and authorities.

Donor-Derived Infections: Monitoring of Posttransplant Infections and Safety Lessons From the Opioid Epidemic.

The inadequate supply of transplantable organs necessitates new approaches to donor screening while avoiding transmission of infections. Donor-derived infections are well described. Multiple changes have occurred in donor management and organ utilization, including increased recognition of and therapies for viral infections, the emergence of multidrug antimicrobial-resistant organisms, and identification of some uncommon viral infections transmitted with allografts to clusters of recipients. Donor evaluation has been impacted by substance use-associated deaths and routine use of serologies and nucleic acid testing for hepatitis C virus, hepatitis B virus, and human immunodeficiency virus. Improved assays are needed to prevent infectious transmissions. The MGH Transplant Center reviewed experience with recipients of organs from donors meeting donor risk criteria and tracked all recipients for possible exposures to hepatitis C virus, hepatitis B virus, and human immunodeficiency virus. This required development of an electronic database to document microbiologic testing data. Database enhancements allowed tracking of serologic testing. Among our organ recipients, no transmissions of the studied viruses were identified by nucleic acid testing or clinically. Multiple patients had positive serologic assays for tested viruses; all recipients were retested, and appropriate interventions were introduced if the test was confirmed. Some false-positive serologies resulted from recent hepatitis B virus vaccination, receipt of blood products, or transmission of donor B cells with tissues. Organ transplant from donors meeting donor risk criteria for disease transmission can be performed safely with appropriate informed consent and rigorous pre- and posttransplant microbiological testing. Enhanced compliance with vaccination for hepatitis B virus should be tracked. New sequencing technologies developed for investigation of undiagnosed infections and in xenotransplantation may inform future directions for donor screening. Such tools may increase the safe utilization of organs from donors who have potential risk for transmission of infection to recipients.

Dengue and COVID-19: Managing Undifferentiated Febrile Illness during a "Twindemic".

Background: During the COVID-19 pandemic, distinguishing dengue from COVID-19 in endemic areas can be difficult, as both may present as undifferentiated febrile illness. COVID-19 cases may also present with false-positive dengue serology. Hospitalisation protocols for managing undifferentiated febrile illness are essential in mitigating the risk from both COVID-19 and dengue. Methods: At a tertiary hospital contending with COVID-19 during a dengue epidemic, a triage strategy of routine COVID-19 testing for febrile patients with viral prodromes was used. All febrile patients with viral prodromes and no epidemiologic risk for COVID-19 were first admitted to a designated ward for COVID-19 testing, from January 2020 to December 2021. Results: A total of 6103 cases of COVID-19 and 1251 cases of dengue were managed at our institution, comprising a total of 3.9% (6103/155,452) and 0.8% (1251/155,452) of admissions, respectively. A surge in dengue hospitalisations in mid-2020 corresponded closely with the imposition of a community-wide lockdown. A total of 23 cases of PCR-proven COVID-19 infection with positive dengue serology were identified, of whom only two were true co-infections; both had been appropriately isolated upon admission. Average length-of-stay for dengue cases initially admitted to isolation during the pandemic was 8.35 days (S.D. = 6.53), compared with 6.91 days (S.D. = 8.61) for cases admitted outside isolation (1.44 days, 95%CI = 0.58–2.30, p = 0.001). Pre-pandemic, only 1.6% (9/580) of dengue cases were admitted initially to isolation-areas; in contrast, during the pandemic period, 66.6% (833/1251) of dengue cases were initially admitted to isolation-areas while awaiting the results of SARS-CoV-2 testing. Conclusions: During successive COVID-19 pandemic waves in a dengue-endemic country, coinfection with dengue and COVID-19 was uncommon. Routine COVID-19 testing for febrile patients with viral prodromes mitigated the potential infection-prevention risk from COVID-19 cases, albeit with an increased length-of-stay for dengue hospitalizations admitted initially to isolation.

Misleading Positive Serology for Cat Scratch Disease following Administration of Intravenous Immunoglobulin.

Cat scratch disease (CSD), caused by Bartonella henselae, usually presents as regional lymphadenopathy/lymphadenitis, known as typical CSD or as atypical CSD, which includes, among others, neurological manifestations. Serology for anti-B. henselae IgG antibodies is the most commonly used diagnostic tests for CSD. Intravenous immunoglobulin (IVIG) is given for an increasing number of medical conditions and may cause interference with serological testing. We report six patients with neurological manifestations and two patients with Kawasaki disease mimicking typical CSD, mistakenly diagnosed as CSD due to false-positive serology following IVIG therapy. Bartonella IgG serology was positive one to six days after IVIG administration and reverted to negative in seven of eight patients or significantly decreased (1 patient) ≤30 days later. In patients with CSD, IgG titers remained essentially unchanged 15–78 days after the positive serum sample. An additional eight patients treated with IVIG for various conditions were evaluated prospectively. All were seronegative one day pre-IVIG infusion, five patients demonstrated an increase in the IgG titers one to three days after IVIG administration, one interpreted as positive and four as intermediate, whereas three patients remained seronegative, suggesting that false seropositivity after IVIG therapy may not occur in all patients. Treatment with IVIG can result in false-positive serology for B. henselae. Increased awareness to the misleading impact of IVIG is warranted to avoid misinterpretation. Repeat testing can distinguish between true and false serology. Preserving serum samples prior to IVIG administration is suggested.

Who Could Be Blamed in the Case of Discrepant Histology and Serology Results for Helicobacter pylori Detection?

Background. Discrepancies between histology and serology results for Helicobacter pylori detection could be caused by a variety of factors, including a biopsy sampling error, expertise of the pathologist, natural loss of infection due to advanced atrophy, or a false-positive serology in the case of a previous infection, since antibodies may be present in blood following recovery from the infection. Aims. To identify true H. pylori-positive individuals in discrepant cases by serology and histology using real time polymerase chain reaction (RT-PCR) as a gold standard. Methods. Study subjects with discrepant histology and serology results were selected from the GISTAR pilot study data base in Latvia. Subjects having received previous H. pylori eradication therapy or reporting use of proton pump inhibitors, antibacterial medications, or bismuth containing drugs one month prior to upper endoscopy were excluded. We compared the discrepant cases to the corresponding results of RT-PCR performed on gastric biopsies. Results. In total, 97 individuals with discrepant results were identified: 81 subjects were serology-positive/histology-negative, while 16 were serology-negative/histology-positive. Among the serology-positive/histology-negative cases, 64/81 (79.0%) were false-positives by serology and, for the majority, inflammation was absent in all biopsies, while, in the serology-negative/histology-positive group, only 6.2% were proven false-positives by histology. Conclusions. Among this high H. pylori prevalent, middle-aged population, the majority of discrepant cases between serology and histology were due to false positive-serology, rather than false-negative histology. This confirms the available evidence that the choice of treatment should not be based solely on the serological results, but also after excluding previous, self-reported eradication therapy.

Covid-19 and dengue fever combine infection, a dangerous combination for the health system of Pakistan

As the world struggles to deal with the consequences of the COVID-19 pandemic, dengue fever endemic regions are facing the threat of a double pandemic that might totally overwhelm administrations of health care service. In Latin America and Asia, simultaneous epidemics of dengue and COVID-19, as well as possible instances of co-infections, have already begun. Because the healthcare system is already stretched enough, a fatal combination like this may devastate hospital emergency departments and the economy as a whole. Frontline clinicians must use precise epidemiological and contact history-taking techniques, as well as pay close attention to false-positive dengue serology and the possibility of co-infections, to tackle this apparently overwhelming obstacle. Key words: Covid-19; Dengue fever; Co-infection; health system

High prevalence of false positive SARS-CoV2 serology in a cohort of patients with liver autoimmune diseases

Aim Monitoring the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) immunization in patients with autoimmune diseases is of particular concern to understand their response to the infection and to the vaccine. In fact, the immunological disorder and the immunosuppressive therapies could affect the serological response. SARS-CoV2 serological tests potentially provide this information, although they were rapidly commercialized with internal verifications. Here, we analysed the seroprevalence to SARS-CoV2 in a cohort of patients with liver autoimmune diseases. Methods From May to December 2020, a cohort of patients affected by primary biliary cholangitis (PBC), autoimmune hepatitis (AIH) and PBC/AIH overlap syndrome were screened with (reverse transcription-polymerase chain reaction) RT-PCR of nasopharyngeal swabs, rapid antigenic test and chemiluminescent serological test during routine follow-up. Results The analysis of 42 patients was carried out: 18 (42.85%) PBC, 12 (28.57%) AIH and 12 (28.57%) PBC/AIH overlap syndromes. Only 2 patients (4.76%) resulted positive to the RNA, antigen and antibody detection tests, hence affected by SARS-CoV2 infection. 14 subjects out of 40 negative cases presented a positive serology for SARS-CoV2 antibodies, hence with a false positivity in the 35% of cases without infection. Among these, 6 (42.86%) patients presented only immunoglobulin (Ig)M positivity, 6 (42.86%) patients presented positivity for only IgG and 2 (14.28%) patients were positive to both IgM and IgG. Notably, the presence of autoantibodies did not correlate with the serological false positivity, highlighting that there is no cross-reactivity with autoantibodies. The presence of polyclonal hypergammaglobulinemia did not interfere with the serological test as well. Interestingly, the patients with false positive serology showed higher levels of gamma-glutamyltransferase (GGT) and C-reactive protein (CRP). Conclusions Patients with liver autoimmune diseases present a high rate of false positive SARS-CoV2 serology. Therefore, new strategies are needed to study the serological response in this patient category.

False-positive HIV serology, Candida lusitaniae pneumonia, and a novel mutation in the CYBB gene

BackgroundChronic granulomatous disease (CGD) presents with a myriad of clinical manifestations pertaining to both immunodeficiency and hyperinflammation. Although Candida infection is a signature organism for patients with CGD, C. lusitaniae pneumonia in CGD has rarely been reported. C. lusitaniae is a ubiquitous ascomycete predominantly infecting immunocompromised hosts and has the potential to rapidly develop multi-drug resistance during therapy. Additionally, C. lusitaniae is recognized for its variable resistance against amphotericin B. To date, C. lusitaniae infections in patients with CGD have not been reviewed in detail. False-positive HIV serology, resulting from polyclonal hypergammaglobulinemia, has been reported in association with several infections, auto-immune diseases, and malignancies. Although CGD is often associated with hypergammaglobulinemia, a false-positive HIV serology in CGD has not been reported previously. ProcedureWe report a combination of unique findings in a child with CGD – a false-positive HIV serology, Candida lusitaniae pneumonia, and a novel CYBB mutation. We also provide a detailed review of C. lusitaniae infections in patients with CGD. ResultsIn patients with CGD, C. lusitaniae has been reported to cause lymphadenitis (cervical, abdominal), fungemia, meningoencephalitis, or abscesses in the liver and spleen. Many CGD patients with C. lusitaniae infection have associated inflammatory complications of the gut (inflammatory bowel disease, colitis). Additionally, almost all C. lusitaniae infections in CGD have been reported in young infants or in patients receiving long-term immunosuppressive therapy. This reflects that further immunocompromise (in addition to the underlying immune deficiency in CGD) may specifically predispose to C. lusitaniae infection (unlike other candidal infections). Most of the CGD patients with documented C. lusitaniae infection have X-linked form of the disease which generally has been postulated to have a more severe clinical phenotype than the autosomal recessive forms of the disease. ConclusionsHIV serology may be positive in patients with CGD and other inborn errors of immunity as a result of hypergammaglobulinemia. C. lusitaniae, which may have peculiar and evolving antimicrobial sensitivity patterns, needs to be considered in patients with CGD and pneumonia. Lastly, to reiterate, CGD should to be considered in patients with proven C. lusitaniae infection.

Low Titer Tissue Transglutaminase Antibodies: A Link to Helicobacter pylori Infection?

Introduction: Low serum titer of anti-tissue transglutaminase (tTG) has been described in various conditions without any evidence of celiac disease (CD). Infectious agents have been suggested to trigger autoimmunity and promote the production of anti-tTG. The aim of this study was to investigate if there is a link between a positive celiac serology and concomitant Helicobacter pylori infection in children. Methods: The data of 178 pediatric patients who underwent upper gastrointestinal endoscopy due to positive celiac serology were compiled. The patients whose histopathologic findings were not consistent with CD were followed on gluten-containing diet. The changes in the serum level of anti-tTG IgA on the follow-up were compared between H. pylori-infected and noninfected patients after the eradication of H. pylori. Results: Of 155 patients who met the inclusion criteria, 119 (group 1) were diagnosed as CD, and duodenal histopathology of the remaining 36 children (group 2) was not compatible with CD. In group 2, 11 out of 36 (30.5%) patients were infected with H. pylori. After the eradication of H. pylori, anti-tTG IgA level either decreased or dropped below cutoff value in 9/11 (81%) patients while it was 20% in those who were not infected with H. pylori in the 6th month of the follow-up (p = 0.001). Conclusion: Our results suggest that H. pylori infection may be the cause of false or transient positive celiac serology. Thus, a positive celiac serology should be carefully interpreted in the presence of H. pylori infection before confirming the diagnosis of this life-long disease.

False Positive Hepatitis C Virus Serologies in Pediatric Patients with Left Ventricular Assist Devices

Introduction Left ventricular assist devices (LVAD) are being used more frequently in pediatric patients with advanced heart failure as a bridge to transplant. Pediatric centers began implanting the HeartMate 3 LVAD in 2017 and it has become the LVAD of choice at many centers, including our own. Allosensitization is commonly observed after LVAD placement, resulting in higher frequencies of auto-antibodies, though the pathophysiology of this phenomenon is not well understood. Viral hepatitis screening is done prior to transplant, but there are no current guidelines on type of testing and timing with regards to LVAD placement. Case Report Three pediatric patients, aged 7-12 years old, each received an LVAD as bridge to orthoptic heart transplant (OHT) between May 2019 - September 2020. All were otherwise healthy and had negative hepatitis C (HCV) antibody tests prior to Heartmate 3 LVAD placement as part of the pre-transplant infectious work up. Repeat HCV serologic testing obtained shortly before cardiac transplant were positive in all three patients. The patients had no signs or symptoms of acute HCV infection, received infrequent blood transfusions between LVAD placement and OHT, and had no increased risk behaviors. Concurrent HCV quantitative PCR testing was done in two patients and both were negative. HCV antibody testing repeated within six weeks from LVA removal was negative in all three patients. Summary False positive HCV serology secondary to immunogenicity of LVADs has been described in adult literature. Our case series is the first, to our knowledge, to be described in pediatric patients. Adult data suggests that the false positive HCV serology can occur in 16-59% of cohorts post-LVAD. This is thought to be due to immunogenicity of the LVAD as serologies revert after the LVAD is explanted. Our experience demonstrates the importance of standardizing HCV testing in patients both pre- and post-LVAD as a bridge to OHT. Furthermore, acquisition of hepatitis C infection is rare in children and pediatric cardiac transplant providers should be aware of the possibility of false positive HCV antibody tests in this clinical scenario and the importance of confirmatory testing with quantitative PCR if concerned.

A high prevalence of potential HIV elite controllers identified over 30 years in Democratic Republic of Congo

BackgroundIn-depth analysis of the HIV pandemic at its epicenter in the Congo basin has been hampered by 40 years of political unrest and lack of functional public health infrastructure. In recent surveillance studies (2017-18), we found that the prevalence of HIV in Kinshasa, Democratic Republic of Congo (11%) far exceeded previous estimates.Methods10,457 participants were screened in Kinshasa with rapid tests from 2017-2019. Individuals confirmed as reactive by the Abbott ARCHITECT HIV Ag/Ab Combo assay (n=1968) were measured by the Abbott RealTime HIV-1 viral load assay. Follow up characterization of samples was performed with alternate manufacturer viral load assays, qPCR for additional blood borne viruses, unbiased next generation sequencing, and HIV Western blotting.FindingsOur data suggested the existence of a significant cohort (n=429) of HIV antibody positive/viral load negative individuals. We systematically eliminated collection site bias, sample integrity, and viral genetic diversity as alternative explanations for undetectable viral loads. Mass spectroscopy unexpectedly detected the presence of 3TC antiviral medication in approximately 60% of those tested (209/354), and negative Western blot results indicated false positive serology in 12% (49/404). From the remaining Western blot positives (n=53) and indeterminates (n=31) with reactive Combo and rapid test results, we estimate 2.7-4.3% of infections in DRC to be potential elite controllers. We also analyzed samples from the DRC collected in 1987 and 2001-03, when antiretroviral drugs were not available, and found similarly elevated trends.InterpretationViral suppression to undetectable viral loads without therapy occurs infrequently in HIV-1 infected patients around the world. Mining of global data suggests a unique ability to control HIV infection arose early in central Africa and occurs in <1% of founder populations. Identification of this group of elite controllers presents a unique opportunity to study potentially novel genetic mechanisms of viral suppression.FundingAbbott Laboratories funded surveillance in DRC and subsequent research efforts. Additional funding was received from a MIZZOU Award from the University of Missouri. Research was supported in part by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, NIH.

COVID-19 patient's false-positive seropositivity with Typhoid fever serodiagnostic tests

The clinical spectrum of coronavirus disease 2019 (COVID-l9) varies from asymptomatic or paucisymptomatic forms to clinical conditions characterised by respiratory failure that necessitates mechanical ventilation and support in an ICU, to multiorgan and systemic manifestations in terms of sepsis, septic shock, and multiple organ dysfunction syndromes (MODS). Typhoid fever is a global health problem, and it is endemic in the developing world, especially the South and South-East Asian countries of India, Nepal, Pakistan, Bangladesh, Vietnam, and Indonesia. Now during this COVID-19 pandemic, the false-positive Widal test in COVID-19 patients is significant public health issue for developing world. During March 2020 in Singapore, false-positive dengue serology in COVID-19 patients were reported. Now typhoid and dengue false-positive in serological test should be interpreted with caution and requires surveillance and continuous follow-up of these patients during COVID-19 pandemic. The six patients in India with false-positive results from Widal testing for Typhoid fever, who were later, confirmed to have COVID-19 infection. The causative virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), it was confirmed by RT-PCR and classical changes in the chest CT scans. Now the Dengue, Typhoid and Malaria along with COVID-19 during this pandemic are a big challenge for clinicians, public health experts and governments in the developing world.

COVID-19 Patient’s False-Positive Seropositivity with Typhoid Fever Serodiagnostic Tests.

The clinical spectrum of coronavirus disease 2019 (COVID-l9) varies from asymptomatic or paucisymptomatic forms to clinical conditions characterised by respiratory failure that necessitates mechanical ventilation and support in an ICU, to multiorgan and systemic manifestations in terms of sepsis, septic shock, and multiple organ dysfunction syndromes (MODS). Typhoid fever is a global health problem, and it is endemic in the developing world, especially the South and South-East Asian countries of India, Nepal, Pakistan, Bangladesh, Vietnam, and Indonesia. Now during this COVID-19 pandemic, the false-positive Widal test in COVID-19 patients is significant public health issue for developing world. During March 2020 in Singapore, false-positive dengue serology in COVID-19 patients were reported. Now typhoid and dengue false-positive in serological test should be interpreted with caution and requires surveillance and continuous follow-up of these patients during COVID-19 pandemic. The six patients in India with false-positive results from Widal testing for Typhoid fever, who were later, confirmed to have COVID-19 infection. The causative virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), it was confirmed by RT-PCR and classical changes in the chest CT scans. Now the Dengue, Typhoid and Malaria along with COVID-19 during this pandemic are a big challenge for clinicians, public health experts and governments in the developing world.

HIV false positive screening serology due to sample contamination reduced by a dedicated sample and platform in a high prevalence environment.

Automated testing of HIV serology on clinical chemistry analysers has become common. High sample throughput, high HIV prevalence and instrument design could all contribute to sample cross-contamination by microscopic droplet carry-over from seropositive samples to seronegative samples resulting in false positive low-reactive results. Following installation of an automated shared platform at our public health laboratory, we noted an increase in low reactive and false positive results. Subsequently, we investigated HIV serology screening test results for a period of 21 months. Of 485 initially low positive or equivocal samples 411 (85%) tested negative when retested using an independently collected sample. As creatinine is commonly requested with HIV screening, we used it as a proxy for concomitant clinical chemistry testing, indicating that a sample had likely been tested on a shared high-throughput instrument. The contamination risk was stratified between samples passing the clinical chemistry module first versus samples bypassing it. The odds ratio for a false positive HIV serology result was 4.1 (95% CI: 1.69-9.97) when creatinine level was determined first, versus not, on the same sample, suggesting contamination on the chemistry analyser. We subsequently issued a notice to obtain dedicated samples for HIV serology and added a suffix to the specimen identifier which restricted testing to a dedicated instrument. Low positive and false positive rates were determined before and after these interventions. Based on measured rates in low positive samples we estimate that before the intervention, of 44 117 HIV screening serology samples, 753 (1.71%) were false positive, declining to 48 of 7 072 samples (0.68%) post-intervention (p<0.01). Our findings showed that automated high throughput shared diagnostic platforms are at risk of generating false-positive HIV test results, due to sample contamination and that measures are required to address this. Restricting HIV serology samples to a dedicated platform resolved this problem.