Serological Antibody Research Articles

Validation of the Diabetomics CovAB SARS-CoV-2 antibody test in children: comparison with serology.

Recently a study determining the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in unvaccinated children in NJ (Katic et al. 2023. Pediatric Academic Societies Meeting; Washington, D.C. https://2023.pas-meeting.org/searchbyposterbucket.asp?bm=Public+Health+%26+Prevention&t=Public+Health+%26+Prevention&pfp=Track) was conducted using a gum swab method for antibody detection. The Diabetomics CovAB test, which qualitatively identifies antibodies to SARS-CoV-2 spike protein, is a point-of-care, low-cost test, that is easy to administer in children. While this test provides sensitive and specific results in adults [US Food and Drug Administration (FDA). 2022. Center for devices and radiological health. EUA authorized serology test performance. Available from: https://www.fda.gov/medical-devices/covid-19-emergency-use-authorizations-medical-devices/eua-authorized-serology-test-performance], data on its accuracy in children is lacking. As a follow-up to the above-mentioned study, we compared the results of the gum swab test to a serologic antibody test. We found that the gum swab test was inferior to serology but was fairly sensitive and specific with a high positive predictive value. While the test is not ideal for diagnostic purposes in children it can be a valuable tool for public health officials and pediatricians to understand the extent of past health interventions.

Rocky Mountain Spotted Fever Encephalitis and "Starry Sky" Pattern on MRI: A Case Report.

Rocky Mountain Spotted Fever (RMSF) is a tick-borne disease caused by Rickettsia rickettsii (R. rickettsii). RMSF presents after a tick bite with fever, rash, and headache but can also cause more serious neurological manifestations. We report a case of RMSF encephalitis presenting with altered sensorium and rapid progression to coma, fever, and petechial rash, and an magnetic resonance imaging (MRI) brain notable for a "starry sky" pattern. A 61-year-old woman presented with confusion and fever and was diagnosed with a urinary tract infection. Two days later, she became comatose. MRI brain revealed lacunar infarcts in the right centrum semiovale and splenium of the corpus callosum. Lumbar puncture was notable for neutrophilic pleocytosis and elevated protein with negative bacterial and viral cultures. Empiric meningitis therapy was initiated, and she was transferred to our institution. On transfer, she was febrile, comatose, and had a diffuse petechial rash. Repeat MRI brain demonstrated diffuse, innumerable punctate foci of diffusion restriction with susceptibility-weighted signal attenuation throughout cerebral hemispheres in a "starry sky" pattern. Skin biopsy revealed perivascular lymphocytic infiltrates. Serologic RSMF antibody titers were obtained, and doxycycline was initiated for presumed RMSF encephalitis. The family opted to pursue palliative measures, given no clinical improvement. RSMF titers and postmortem PCR from brain tissue were positive for R. rickettsii. This case report highlights the clinical presentation of RMSF encephalitis. RMSF encephalitis should be suspected in a patient presenting with encephalopathy, fever, petechial rash, and MRI brain findings of diffuse punctate foci of diffusion restriction and susceptibility-weighted signal attenuation in a "starry-sky" pattern.

The Role of Macrophages in the Pathogenesis of Celiac Disease

Aim: to present data on the involvement of macrophages in the pathogenesis of celiac disease and the development of possible treatment methods for this disease aimed at changing the function of macrophages.Key points. Celiac disease is an autoimmune disease with a characteristic serological (antibodies to tissue transglutaminase, endomysium, deamidated gliadin peptides) and histological profile (inflammatory infiltration of the villous epithelium by lymphocytes and their atrophy, crypt hyperplasia) caused by gluten consumption in genetically predisposed individuals. Macrophages, as key cells that provide a link between innate and adaptive immunity, are of significant importance in the pathogenesis of celiac disease. Gliadin peptides stimulate the activation of macrophages according to the proinflammatory phenotype with the production of cytokines, which causes the immune response of T-helpers 1 and T-helpers 17. The result of these processes is the development of an inflammatory reaction and damage to the intestinal mucosa due to the production of matrix metalloproteinases and reactive oxygen species by macrophages. Therapeutic tactics for celiac disease today include a gluten-free diet, which is not so easy to follow. Of interest is the study of the possibility of using polyphenols in celiac disease, which are capable of precipitating gliadins and inhibiting the polarization of macrophages towards a proinflammatory phenotype, while simultaneously stimulating an increase in the population of macrophages of an anti-inflammatory phenotype associated with a decrease in tissue damage.Conclusion. Impaired macrophage function/differentiation results in either inadequate, excessive immune activation or failure to mount effective protective immune responses against pathogens, which may result in the development of gastrointestinal diseases. Studying the involvement of macrophages at different stages of celiac disease progression is important for the development of new treatments for this disease.

Evaluation of a novel biplex rapid diagnostic test for antibody responses to Loa loa and Onchocerca volvulus infections.

Endemic to Central Africa, loiasis, caused by the vector-borne worm Loa loa, affects approximately 10 million individuals. Clinical manifestations include transient angioedema (Calabar swellings), migration of the adult worm under the eye conjunctiva (eye worm) and less specific general symptoms. Loiasis presents a significant public health challenge because L. loa-infected individuals can develop serious adverse events after taking ivermectin, the drug used to combat onchocerciasis. In this context, alternative interventions and rigorous diagnostic approaches are needed. Diagnosing loiasis is challenging because its main clinical manifestations are sporadic and non-specific. The definitive diagnosis relies on identifying adult worms migrating beneath the conjunctiva, or microfilariae (pre-larvae) in blood smears. However, "occult loiasis" (infection without blood microfilariae) is frequent. Serological rapid antibody diagnostic tests (ARTs) can provide an alternative diagnostic method. We compared a novel ART simultaneously targeting onchocerciasis (IgG4 to Ov-16 and OvOC3261, test line 1) and loiasis (IgG4 to L1-SXP-1, test line 2), called IgG4-SXP-1 biplex test) to the already established Loa-ART (all IgG isotypes to Ll-SXP-1, called pan-IgG-SXP-1 test). Blood samples underwent both ARTs, read qualitatively and semi-quantitatively. Additionally, blood smears, skin snips, Kato-Katz method for soil-transmitted helminthiases identification and eosinophilia measurements were performed. Questionnaires gathered demographic details and loiasis-related signs. ARTs performance was compared using specific loiasis-related signs and microfilaremia as references. Discordances between the two ARTs were investigated using logistic regression models. Out of 971 participants, 35.4% had L. loa microfilaremia, 71.9% had already experienced loiasis-related signs, 85.1% were positive in the pan-IgG-SXP-1 test and 79.4% were positive in the IgG4-SXP-1 biplex test. In the microfilariae-positive population, the sensitivity of the rapid tests was 87.4% for the pan-IgG-SXP-1 test and 88.6% for the prototype IgG4-SXP-1 biplex test. Sensitivity was similar for both ARTs when using eye worm or Calabar swelling as references, but diagnostic performance varied based on microfilaremia levels and occult loiasis. Overall, IgG4-SXP-1 biplex test demonstrated a sensitivity of 84.1% and specificity of 47.6% for loiasis compared to the pan-IgG-SXP-1 test, leading to a Kappa coefficient estimated at 0.27 ± 0.03 for the qualitative results of the 2 ARTs. In the group that tested positive with the Pan-IgG test but negative with the IgG4-specific test, there was a lower prevalence of STH infection (p = 0.008) and elevated eosinophilia (p<0.001) compared to the general tested population. The sensitivity of each test was good (84-85%) but the diagnostic agreement between the two ARTs was poor, suggesting that IgG and IgG4 antibody responses should be interpreted differently. The assessment of the innovative rapid diagnostic IgG4-SXP-1 biplex test, designed for onchocerciasis and loiasis, shows encouraging sensitivity but underlines the necessity for further in vitro assessment.

Seroprevalence Of Crimean Congo Hemorrhagic Fever in Cattle in Thi-qar Province, Iraq

Crimean–Congo Hemorrhagic Fever is a zoonotic disease that transmission by infected ticks bites and from animals that are main carrier host without clinical septum so the current study was aimed to serological detection antibodies of Crimean–Congo Hemorrhagic Fever virus (CCHV) in cattle of Thi-qar province. Sera were analyzed for the presence of antibodies to CCHFV using the commercially available double-antigen ELISA kit. The study was conducted on 262 cases of cattle (87 male and 175 female) infected with CCHF based on Infected with ticks. Blood samples were collected from different part in Thi-qar province AL-Rifai, AL-Shatra, AL- Naser and Suq-ALshuhk. The wholly percentage of infected cattle with antibodies was 169(64.5%) positive from 262 cases. Highly prevalence record in Al-shatra positive from150 \115positive (76.66%) The prevalence of antibodies was higher in cattle at age 2 to 3 years old 55(73.33%) than in cattle aged less than 2 years 49 (58.33%). In addition, the percentage of cattle with antibodies in female was higher compare in male. These results suggest that is (CCHV) widespread in the cattle populations southern of Iraq.

Maternal Cytomegalovirus (CMV) Serology: The Diagnostic Limitations of CMV IgM and IgG Avidity in Detecting Congenital CMV Infection.

Congenital cytomegalovirus (cCMV) is a common congenital viral infection. Testing for cCMV usually begins with assessing maternal CMV serology, specifically IgM and IgG antibodies. A negative maternal CMV IgM suggests a low risk of recent maternal CMV infection, thereby suggesting a low risk of cCMV in the fetus. Consequently, cCMV is often ruled out when maternal CMV IgM is negative. In our perinatal autopsy and placental pathology database, we identified 5 cases of cCMV despite negative maternal CMV IgM results in the second trimester. In all 5 cases, fetal abnormalities were first detected by ultrasound in the second trimester, prompting maternal CMV testing. Since second trimester maternal CMV IgM was negative in all cases, cCMV was considered unlikely, thus precluding further prenatal CMV testing in 4 of these cases. The diagnosis of cCMV was subsequently made through placental and/or autopsy examinations. Following this diagnosis, retrospective CMV serology and IgG avidity testing was performed on stored frozen first-trimester maternal blood samples in 3 cases. Among these, the first-trimester samples in 2 cases were IgG+, IgM+, and exhibited low IgG avidity, suggesting a primary maternal CMV infection around the time of conception. In the third case, both first and second-trimester maternal blood samples were IgG+, IgM-, and showed high IgG avidity, suggesting a non-primary maternal CMV infection (i.e., reactivation or reinfection of CMV). A negative maternal CMV IgM in the second trimester cannot exclude cCMV infection. While CMV IgG avidity testing and analysis of stored frozen first-trimester maternal blood samples provide valuable insights, they have limitations. CMV PCR performed on amniotic fluid is a useful prenatal diagnostic tool. For cases of unexplained fetal abnormalities or death, autopsy and placental examination are recommended.

Integrated Serosurveillance for Onchocerciasis, Lymphatic Filariasis, and Schistosomiasis in North Darfur, Sudan.

Sudan is endemic for multiple neglected tropical diseases, including trachoma, onchocerciasis (OV), lymphatic filariasis (LF), and schistosomiasis (SCH). In 2019, dried blood spot samples were collected for a baseline trachoma serosurvey in three localities (El Seraif, Kotom, and Saraf Omrah) in North Darfur State. None were classified previously as OV- or LF-endemic, although low levels of SCH had been identified in all three. Approximately 30 households from 25 communities in each locality were selected by multistage cluster random sampling. Collections of DBSs were analyzed by multiplex bead assay for antibodies to multiple pathogens. This paper presents data on OV (Ov16), LF (Wb123, Bm14, Bm33), and SCH (soluble egg antigen [SEA], Sm25) antibodies among 8,322 individuals from 2,119 households. The survey-adjusted seroprevalence estimates for Ov16 were <0.3% in all localities. Lymphatic filariasis-antigen seroprevalences were discordant. Seroprevalence estimates ranged from 4.6-6.0% (Wb123), 0.99-1.4% (Bm14), and 29.2-33.3% (Bm33). Schistosomiasis seroprevalence estimates among school-aged children ranged from 2.7-8.0% (SEA) and 10.9-15.6% (Sm25). Ov16 seropositivity was low and supported the localities' classification as nonendemic. The results suggested LF exposure, but discordance between antigens, challenges defining seropositivity thresholds, and the absence of programmatic guidance based on antibody serology alone for Wuchereria bancrofti indicate a need for remapping surveys to confirm transmission. Schistosomiasis antibody levels were high enough to warrant further mapping to guide treatment decisions. The lack of gold standards limited interpretation of results, particularly for LF, but in resource-challenged areas, integrated serological surveillance offers the possibility of efficient monitoring of exposure to multiple diseases.

ADAPTATION OF A COMMERCIALLY AVAILABLE WESTERN BLOT KIT FOR THE DETECTION OF ANTIBODY TO ASPERGILLUS IN PENGUINS IN FRANCE AND THE UNITED STATES.

Antemortem serodiagnosis of aspergillosis remains challenging in Sphenisciformes. Protein electrophoresis, serology (antibody, antigen) by ELISA, and gliotoxin detection provide variable diagnostic value. In the present study, a commercially available Western blot (WB) validated for use in humans and dolphins was adapted for use with penguin samples. Using the same method and reagents, samples were analyzed from multiple institutions in the United States and one facility in France. This was inclusive of normal juvenile African penguins (Spheniscus demersus, n = 10) and various species of penguins in the United States with confirmed infection (n = 9) as well as 52 samples from Humboldt penguins (Spheniscus humboldti) in France. Cumulative WB scores (based on reactivity to different antigens) were found to be significantly higher in the group of penguins with confirmed infection (p < 0.0001). Significant differences were also observed between the clinically normal penguins in the two populations, with higher scores in the United States (median score 1.0, 95%CI [0-5], min 0, max 11) compared to France (median score 0,95%CI [0-0], min 0, max 5). The utilization of the WB as a diagnostic tool is inconclusive due to the use of samples from varying institutions, environmental background, age, and stages of infection. However, this tool may provide an overview of antigen reactivity in penguins infected with Aspergillus to help design a more robust serology assay and further understand the humoral immune response during infection.

First Detection of Hepatitis B Virus Subgenotype A5, and Characterization of Occult Infection and Hepatocellular Carcinoma-Related Mutations in Latin American and African Immigrants in Brazil.

This study aims to characterize the molecular profile of the hepatitis B virus (HBV) among socially vulnerable immigrants residing in Brazil to investigate the introduction of uncommon HBV strains into the country. Serum samples from 102 immigrants with positive serology for the HBV core antibody (anti-HBc) were tested for the presence of HBV DNA by PCR assays. Among these, 24 were also positive for the HBV surface antigen (HBsAg). The full or partial genome was sequenced to determine genotype by phylogenetic analysis. Participants were from Haiti (79.4%), Guinea-Bissau (11.8%), Venezuela (7.8%), and Colombia (1%). Of the 21 HBV DNA-positive samples, subgenotypes A1 (52.4%), A5 (28.6%), E (9.5%), F2 (4.8%), and F3 (4.8%) were identified. Among the 78 HBsAg-negative participants, four were positive for HBV DNA, resulting in an occult HBV infection rate of 5.1%. Phylogenetic analysis suggested that most strains were likely introduced to Brazil by migration. Importantly, 80% of A5 sequences had the A1762T/G1764A double mutation, linked to an increased risk of hepatocellular carcinoma development. In conclusion, this study is the first report of HBV subgenotype A5 in Brazil, shedding new light on the diversity of HBV strains circulating in the country. Understanding the genetic diversity of HBV in immigrant communities can lead to better prevention and control strategies, benefiting both immigrants and wider society.

The Role of Artificial Intelligence in Predicting Optic Neuritis Subtypes From Ocular Fundus Photographs.

Optic neuritis (ON) is a complex clinical syndrome that has diverse etiologies and treatments based on its subtypes. Notably, ON associated with multiple sclerosis (MS ON) has a good prognosis for recovery irrespective of treatment, whereas ON associated with other conditions including neuromyelitis optica spectrum disorders or myelin oligodendrocyte glycoprotein antibody-associated disease is often associated with less favorable outcomes. Delay in treatment of these non-MS ON subtypes can lead to irreversible vision loss. It is important to distinguish MS ON from other ON subtypes early, to guide appropriate management. Yet, identifying ON and differentiating subtypes can be challenging as MRI and serological antibody test results are not always readily available in the acute setting. The purpose of this study is to develop a deep learning artificial intelligence (AI) algorithm to predict subtype based on fundus photographs, to aid the diagnostic evaluation of patients with suspected ON. This was a retrospective study of patients with ON seen at our institution between 2007 and 2022. Fundus photographs (1,599) were retrospectively collected from a total of 321 patients classified into 2 groups: MS ON (262 patients; 1,114 photographs) and non-MS ON (59 patients; 485 photographs). The dataset was divided into training and holdout test sets with an 80%/20% ratio, using stratified sampling to ensure equal representation of MS ON and non-MS ON patients in both sets. Model hyperparameters were tuned using 5-fold cross-validation on the training dataset. The overall performance and generalizability of the model was subsequently evaluated on the holdout test set. The receiver operating characteristic (ROC) curve for the developed model, evaluated on the holdout test dataset, yielded an area under the ROC curve of 0.83 (95% confidence interval [CI], 0.72-0.92). The model attained an accuracy of 76.2% (95% CI, 68.4-83.1), a sensitivity of 74.2% (95% CI, 55.9-87.4) and a specificity of 76.9% (95% CI, 67.6-85.0) in classifying images as non-MS-related ON. This study provides preliminary evidence supporting a role for AI in differentiating non-MS ON subtypes from MS ON. Future work will aim to increase the size of the dataset and explore the role of combining clinical and paraclinical measures to refine deep learning models over time.

Ethambutol induced subacute cutaneous lupus erythematosus in an elderly female with co-morbidities

Papulosquamous lesions in an elderly female with multiple co-morbidities often pose diagnostic challenge. We present an interesting case of anti-tubercular treatment (ATT) induced sub-acute cutaneous lupus erythematosus. The patient presented with papulosquamous lesions in generalised distribution, which showed interface dermatitis on histopathology. The serology for anti-nuclear antibodies, anti-Ro and anti-La was positive. The rash resolved spontaneously after stopping all the suspected drugs. Oral provocation was performed with first line anti-tubercular drugs and ethambutol was found to be the culprit drug, which was later confirmed by reappearance of skin rash by inadvertent ingestion of one dose of ethambutol by the patient.

Cutaneous lupus subtypes

A broad spectrum of dermatologic manifestations, known as cutaneous lupus erythematosus (CLE), may or may not be linked to the development of systemic disease. There are numerous subtypes of cutaneous lupus, such as acute cutaneous lupus (ACLE), subacute cutaneous lupus (SCLE), and chronic cutaneous lupus (CCLE). CCLE encompasses lupus tumidus, chilblain cutaneous lupus, LE profundus (LEP), and discoid lupus erythematosus (DLE). In order to diagnose these diseases, it is necessary to accurately classify the subtype. This is achieved through a combination of physical examination, laboratory studies, histology, antibody serology, and occasionally direct immunofluorescence, while also excluding systemic disease. The treatment of cutaneous lupus involves the provision of appropriate topical and systemic agents, as well as patient education regarding solar protection. In cases where the disease is pervasive, scarring, or treatment-refractory, systemic agents are recommended. In this chapter, we address the classification and diagnosis of the diverse subtypes of CLE and offer a comprehensive update on therapeutic management.

Analysis of long-lasting tumor-specific antibodies from murine tumors treated with Aliya pulsed electric fields.

e14543 Background: Pulsed electric field (PEF) tissue destruction has demonstrated meaningful systemic immune responses in mice that are superior to thermal ablation, and synergize effectively with systemic chemotherapy and checkpoint blockade (CPB) immunotherapy. Immune cell populations are increased by PEF, including tumor specific activated CD8 T-cells and plasma B-cells. Antitumor immunity can include the presence of circulating anti-cancer antibodies. However, the presence and role of circulating tumor specific antibodies induced by PEF have not been explored. Serological antibodies are often detected with the ELISA assay, where tumor-associated antigens are coated to a microtiter plate to attract the corresponding serum antibodies. Here, we quantify IgG tumor specific antibodies after PEF using an in-house ELISA. Methods: Mice bearing immune-warm (EMT6) and immune-cold (4T1) orthotopic murine breast tumors were treated with a biphasic PEF dose comparable to Aliya titrated for mouse tumors. To detect tumor specific circulating IgG1 immunoglobulin in serum, an ELISA plate was coated with EMT6 and 4T1 protein lysate, as well as with a known 4T1-expressed tumor-specific antigen (gp70). Serum draws from the treated, untreated, and naïve mice were exposed to the coated wells for 1 hour. Bound IgG were detected by anti-mouse IgG (HRP tagged) antibody added to the wells and incubated 1 hour. A TMB substrate was added and color development was allowed for 15 minutes. The optical density was quantified using a microtiter plate reader. Results: ELISA quantification of serum IgG at multiple timepoints show that 4T1 tumor-specific IgG antibodies were increased 14.3- and 2.6-fold by day 20 in the PEF-treated and untreated group survivors relative to Naïve mice, respectively, (OD=0.86 and 0.15 v. 0.06). Furthermore, IgG antibodies specific to the gp70 antigen of the 4T1 cell line were increased by 44.9- and 2.7-fold in the PEF-treated and untreated groups relative to naïve mice (OD=3.14 and 0.19 v. 0.07). In the EMT6 model, at 3 months post-treatment, only the PEF-ablated group mice survived, and showed 15.5-fold higher antibodies against EMT6 tumor antigens compared to naive mice (OD=0.62 v. 0.04). Conclusions: The specific form of PEF in this study generated tumor-specific IgG long-lived antibodies in mice for immune-warm and immune-cold tumor models, corroborating previous findings of increased murine B-cell and plasma cell populations. This effect has not been well-reported for other ablation technologies. Increases were evident by Day 20 post-PEF and persisted at least 3 months. These murine data suggest the PEF used may invoke potent, long-lived immune responses and anti-tumor immune surveillance, offering a potential approach for in situ tumor vaccination to improve metastatic disease outcomes. Future studies should determine response durability and its role in attaining distant tumor clearance.

Chronic Q fever infective endocarditis: a case report

Abstract Q fever is an epidemic disease caused by the Coxiella burnetii (C. burnetii) infection. It can manifest clinically as an acute or chronic disease, with chronic infections being more common. Q fever endocarditis is the most common manifestation of chronic infection and usually occurs in patients with previous valvular heart disease like in our present study, a case of Q fever endocarditis that occurred in background of Tetralogy of Fallot (TOF) surgical repair. However, Q fever endocarditis is difficult to diagnose clinically and may lead to very serious or even life-threatening outcomes if not diagnosed promptly. In the present study, accurate diagnosis and treatment were achieved by 18F-FDG-PET/CT combined with detection of the Q fever serological antibodies.

Serologic Evaluation for Severe Acute Respiratory Syndrome Coronavirus 2 in Pediatric Heart Transplantation Recipients and Patients on a Pediatric Heart Transplantation Waiting List in a Quaternary Hospital

BackgroundThe COVID-19 pandemic has been a global reality for over three years. Serological studies have great importance for the comprehension of the virus's behavior in populations, as it can suggest the status of the epidemic in a community. This cross-sectional study aimed to analyze the serological profile for COVID-19 in patients before and after pediatric heart transplant. MethodsSerologies for IgG and IgM antibodies for Sars-CoV-2 were collected in patients of the Pediatric Cardiology and Congenital Heart Diseases unit of a Brazilian hospital between January and August 2022. In total, 174 patients were recruited: 28 on waiting list and 146 recipients. Information such as demographics (age, gender, state of origin), type of heart disease (congenital or acquired) and time after transplant were analyzed. ResultsOverall, 72 patients had a positive serology for anti-N antibodies (48,0%), being 62 transplant recipients and 10 patients on transplant waiting list, with positivity rates of 48,1% and 47,6%, respectively. Positivity rates for previously infected individuals were 62,5% and 62,1%, respectively. ConclusionsWe found that approximately half of the sample has developed IgM or IgG antibodies against the Sars-CoV-2 virus Serological studies are a relevant tool to public health for health promotion of vulnerable groups, and can be useful to future studies on the antibodies’ behavior. The duration and the level of protection given by these antibodies is still a subject being studied, and can become a key information for the protection of these populations if discovered in the future.

Relationship between HLA genetic variations, COVID-19 vaccine antibody response, and risk of breakthrough outcomes

The rapid global distribution of COVID-19 vaccines, with over a billion doses administered, has been unprecedented. However, in comparison to most identified clinical determinants, the implications of individual genetic factors on antibody responses post-COVID-19 vaccination for breakthrough outcomes remain elusive. Here, we conducted a population-based study including 357,806 vaccinated participants with high-resolution HLA genotyping data, and a subset of 175,000 with antibody serology test results. We confirmed prior findings that single nucleotide polymorphisms associated with antibody response are predominantly located in the Major Histocompatibility Complex region, with the expansive HLA-DQB1*06 gene alleles linked to improved antibody responses. However, our results did not support the claim that this mutation alone can significantly reduce COVID-19 risk in the general population. In addition, we discovered and validated six HLA alleles (A*03:01, C*16:01, DQA1*01:02, DQA1*01:01, DRB3*01:01, and DPB1*10:01) that independently influence antibody responses and demonstrated a combined effect across HLA genes on the risk of breakthrough COVID-19 outcomes. Lastly, we estimated that COVID-19 vaccine-induced antibody positivity provides approximately 20% protection against infection and 50% protection against severity. These findings have immediate implications for functional studies on HLA molecules and can inform future personalised vaccination strategies.

Empirical sample-specific approaches to define HPV16 and HPV18 seropositivity in unvaccinated, young, sexually active women.

Given low seroconversion rates following human papillomavirus (HPV) infection, fixed external cutoffs may lead to errors in estimating HPV seroprevalence. We evaluated finite mixture modeling (FMM) and group-based trajectory modeling (GBTM) among unvaccinated, sexually active, HPV-exposed women to determine study-specific HPV16 and HPV18 seropositivity thresholds. We included 399 women (aged 18-24 years) enrolled in the HPV Infection and Transmission Among Couples Through Heterosexual Activity (HITCH) cohort study between 2005 and 2011 in Montreal, Canada. Participants' blood samples from up to six visits spanning 2 years were tested by multiplex serology for antibodies [median fluorescence intensity (MFI)] specific to bacterially expressed HPV16 and HPV18 L1 glutathione S-transferase fusion proteins. We applied FMM and GBTM to baseline and longitudinal antibody titer measurements, respectively, to define HPV type-specific seronegative and seropositive distributions. Study-specific thresholds were generated as five standard deviations above the mean seronegative antibody titers, mimicking cutoffs (HPV16: 422 MFI; HPV18: 394 MFI) derived from an external population of sexually inactive, HPV DNA-negative Korean women (aged 15-29 years). Agreement (kappa) of study-specific thresholds was evaluated against external cutoffs. Seroprevalence estimates using FMM (HPV16: 27.5%-43.2%; HPV18: 21.7%-49.5%) and GBTM (HPV16: 11.8%-11.8%; HPV18: 9.9%-13.4%) thresholds exceeded those of external cutoffs (HPV: 10.2%; HPV18: 9.7%). FMM thresholds showed slight-to-moderate agreement with external cutoffs (HPV16: 0.26%-0.46%; HPV18: 0.20%-0.56%), while GBTM thresholds exhibited high agreement (HPV16: 0.92%-0.92%; HPV18: 0.82%-0.99%). Kappa values suggest that GBTM, used for longitudinal serological data, and otherwise FMM, for cross-sectional data, are robust methods for determining the HPV serostatus without prior classification rules.IMPORTANCEWhile human papillomavirus (HPV) seropositivity has been employed as an epidemiologic determinant of the natural history of genital HPV infections, only a fraction of women incidentally infected with HPV respond by developing significant antibody levels. HPV seropositivity is often determined by a dichotomous fixed cutoff based on the seroreactivity of an external population of women presumed as seronegative, given the lack of evidence of HPV exposure. However, considering the variable nature of seroreactivity upon HPV infection, which arguably varies across populations, such externally defined cutoffs may lack specificity to the population of interest, causing inappropriate assessment of HPV seroprevalence and related epidemiologic uses of that information. This study demonstrates that finite mixture modeling (FMM) and group-based trajectory modeling (GBTM) can be used to independently estimate seroprevalence or serve as the basis for defining study-specific seropositivity thresholds without requiring prior subjective assumptions, consequently providing a more apt internally valid discrimination of seropositive from seronegative individuals.

Efficacy of Bravecto® Plus spot-on solution for cats (280 mg/ml fluralaner and 14 mg/ml moxidectin) in the prevention of feline Aelurostrongylus abstrusus infection evaluated in a multi-diagnostic approach

BackgroundAelurostrongylus abstrusus is one of the most important respiratory nematodes of felines. Infections may lead to respiratory clinical signs with varying severity or even death, emphasizing the need for preventive treatment of cats with outdoor access to circumvent patent infections.MethodsTherefore, the preventive efficacy of a spot-on formulation of 280 mg/ml fluralaner and 14 mg/ml moxidectin (Bravecto® Plus spot-on solution for cats, MSD) against A. abstrusus was evaluated in a negative controlled, randomized and partially blinded efficacy study with 28 purpose-bred cats in a non-terminal design. In three different treatment regimes, the minimum recommended dose of 40 mg fluralaner and 2.0 mg moxidectin/kg bodyweight (BW) was administered once at 12, 8 or 4 weeks (study group G1, G2 and G3, respectively) prior to experimental infection with 300 third-stage A. abstrusus larvae, while G4 served as placebo-treated control.ResultsFrom 30 to 46 days post infection (dpi; SD 114 to 130), faeces were sampled to monitor first-stage larvae (L1) excretion for efficacy determination. Secondary efficacy criteria, including respiratory parameters, serological antibody levels and computed tomography (CT) findings, were assessed once before enrolment (SD −7 to −1) and before infection (SD 75 to 83). After infection, CT evaluation was performed once at 47–50 dpi (SD 131 to 134), and respiratory parameters and antibody levels were regularly assessed twice or once a week, respectively (1 up to 78 dpi, SD 85 up to 162). All animals in the control group excreted L1 by 33–37 dpi and remained positive throughout the study period from 41 to 46 dpi (SD 125 to 130). In the treatment groups, only one animal each of G1 and G2 excreted L1 at two consecutive days, and four cats of G1, two of G2 and three of G3 were positive on single occasions. While the geometric mean (GM) of the maximum number of excreted L1 per 5 g of faeces was 7380.89 in the control group (G4), GMs were significantly lower in the treatment groups with 1.63 in G1, 1.37 in G2 and 0.79 in G3. Thus, based on GMs, the reduction in excreted L1 exceeded 99.9% in all three treatment groups. Based on CT severity scores, all lungs of the animals of the control group showed severe pulmonary changes post infection, whereas lungs of the cats of the treatment groups were either unaltered (4 animals), mildly (11 animals), or moderately altered (5 animals). Moreover, seroconversion was observed in all cats of the control group, but not in those of the treatment groups.ConclusionsThe combination of diagnostic methods used in this non-terminal study yielded coherent and reliable results. A single administration of Bravecto® Plus spot-on solution for cats was well tolerated and effective in the prevention of aelurostrongylosis for at least 12 weeks.Graphical

Clinical course, management and outcomes of COVID-19 in HIV-infected renal transplant recipients: A case series.

HIV-infected kidney transplant recipients with COVID-19 are at increased risk of acute illness and death owing to their underlying comorbidities and chronic immunosuppression. To describe the incidence, clinical presentation and course of COVID-19, vaccination status, and SARS-CoV-2 antibody positivity rate among HIV-infected-to-HIV-infected kidney transplant recipients in South Africa (SA). This retrospective study reports on rates of SARS-CoV-2 infection, COVID-19 and mortality among SA HIV-infected kidney transplant recipients who received organs from HIV-infected donors (HIV positive to HIV positive), before and after vaccination. Patient demographics, clinical presentation, course, management and disease outcomes were analysed. Antibody serology tests were performed between May and September 2022. Among 39 HIV-positive-to-HIV-positive transplant recipients, 11 cases of COVID-19 were diagnosed from March 2020 to September 2022. Six patients (55%) required hospitalisation, of whom 3 were admitted to a high-care unit or intensive care unit. Two patients required mechanical ventilation, and 2 received acute dialysis. One patient was declined access to intensive care. Four patients (10%) died of COVID-19 pneumonia. All the COVID-19-positive patients had at least one comorbidity. Vaccination data were available for 24 patients, of whom 5 had refused SARS-CoV-2 vaccination. SARS-CoV-2 antibody data were available for 20 patients; 4 vaccinated patients had a negative nucleocapsid protein antibody test and a positive spike protein antibody test, suggesting vaccination-acquired immunity. The remaining 16 patients demonstrated immunity that was probably due to COVID infection, and of these, 14 were also vaccinated. Of the 11 COVID-19 cases, only 1 was observed after vaccination. In our case series, ~10% of the HIV-positive-to-HIV-positive transplant recipients died of COVID-19 pneumonia. This mortality rate appears higher than figures reported in other transplant cohorts. However, it is likely that the actual number of cases of SARS-CoV-2 infection was much higher, as the study only included polymerase chain reaction-confirmed cases. It remains unclear whether HIV infection, transplant or the combination of the two drives poorer outcomes, and larger studies adjusting for important demographic and biological factors may isolate these effects.

Long-term monitoring of SARS-CoV-2 seroprevalence and variants in Ethiopia provides prediction for immunity and cross-immunity

Under-reporting of COVID-19 and the limited information about circulating SARS-CoV-2 variants remain major challenges for many African countries. We analyzed SARS-CoV-2 infection dynamics in Addis Ababa and Jimma, Ethiopia, focusing on reinfection, immunity, and vaccination effects. We conducted an antibody serology study spanning August 2020 to July 2022 with five rounds of data collection across a population of 4723, sequenced PCR-test positive samples, used available test positivity rates, and constructed two mathematical models integrating this data. A multivariant model explores variant dynamics identifying wildtype, alpha, delta, and omicron BA.4/5 as key variants in the study population, and cross-immunity between variants, revealing risk reductions between 24% and 69%. An antibody-level model predicts slow decay leading to sustained high antibody levels. Retrospectively, increased early vaccination might have substantially reduced infections during the delta and omicron waves in the considered group of individuals, though further vaccination now seems less impactful.