Prospective, Randomized, Double-Blind Parallel Group Nutritional Study to Evaluate the Effects of Routine Intake of Fresh vs. Pasteurized Yogurt on the Immune System in Healthy Adults.

The immune system is affected by the dietary products humans intake. Immune system regulation by nutrition has uses in the clinical context, but it can also benefit healthy populations by delaying or preventing the emergence of immune-mediated chronic illnesses. In this study, the purpose was to describe and compare the modulator effects on the immune system of the routine ingestion of fresh vs. pasteurized yogurt. A unicentral, prospective, randomized, double-blind, parallel group 8-week nutritional study was carried out comparing the ingestion of 125 g of the products in healthy adults three times a day. A complete battery of in vitro tests on the activity of the immune system, processes and phenomena was performed. Exclusive immune-modulatory effects of fresh yogurt with respect to base line were found in terms of increased systemic IgM (primary immune responses), increased synthesis of IFN-gamma upon stimulation (Th1) and increased peripheral T cells (mainly "naive" CD4s). In the three interventions, we observed an increased phagocytic activity and burst test in granulocytes, together with increased secretion of IL-6, IL-1 ß and IL-8 (pro-inflammatory) and increased CD16 expression (FcR favoring phagocytosis) in granulocytes. Overall, it is concluded that regardless of bacteria being alive or thermally inactivated, yogurt has common effects on the innate system, but the presence of live bacteria is necessary to achieve a potentiating effect on the specific immune response.

Co-circulation of two Alphaviruses in Burkina Faso: Chikungunya and O'nyong nyong viruses.

BACKGROUND: Chikungunya virus (CHIKV) and O'nyong nyong virus (ONNV) are phylogenetically related alphaviruses in the Semliki Forest Virus (SFV) antigenic complex of the Togaviridae family. There are limited data on the circulation of these two viruses in Burkina Faso. The aim of our study was to assess their circulation in the country by determining seroprevalence to each of the viruses in blood donor samples and by retrospective molecular and serological testing of samples collected as part of national measles and rubella surveillance. METHODOLOGY/PRINCIPAL FINDINGS: All blood donor samples were analyzed on the Luminex platform using CHIKV and ONNV E2 antigens. Patient samples collected during national measles-rubella surveillance were screened by an initial ELISA for CHIKV IgM (CHIKjj Detect IgM ELISA) at the national laboratory. The positive samples were then analyzed by a second ELISA test for CHIKV IgM (CDC MAC-ELISA) at the reference laboratory. Finally, samples that had IgM positive results for both ELISA tests and had sufficient residual volume were tested by plaque reduction neutralization testing (PRNT) for CHIKV and ONNV. These same patient samples were also analyzed by rRT-PCR for CHIKV. Among the blood donor specimens, 55.49% of the samples were positive for alphaviruses including both CHIKV and ONNV positive samples. Among patient samples collected as part of national measles and rubella surveillance, 3.09% were IgM positive for CHIKV, including 2.5% confirmed by PRNT. PRNT failed to demonstrate any ONNV infections in these samples. No samples tested by RT-qPCR. had detectable CHIKV RNA. CONCLUSIONS/SIGNIFICANCE: Our results suggest that CHIKV and ONNV have been circulating in the population of Burkina Faso and may have been confused with malaria, dengue fever or other febrile diseases such as measles or rubella. Our study underscores the necessity to enhance arbovirus surveillance systems in Burkina Faso.

Potential Usefulness of IgA for the Early Detection of SARS-CoV-2 Infection: Comparison With IgM.

Serological testing can be a powerful complementary approach to achieve timely diagnosis of severe acute respiratory coronavirus 2 (SARS-CoV-2) infection, along with nucleic acid detection. Immunoglobulin (Ig) A antibodies are less frequently utilized to detect SARS-CoV-2 infection than IgM and IgG antibodies, even though IgA antibodies play an important role in protective immunity against SARS-CoV-2. This review discusses the differences in kinetics and assay performance between IgA and IgM antibodies and the factors influencing antibody responses. It highlights the potential usefulness of analyzing IgA antibodies for the early detection of SARS-CoV-2 infection. The early appearance of IgA and the high sensitivity of IgA-based immunoassays can aid in diagnosing coronavirus disease 2019. However, because of cross-reactivity, it is important to recognize the only moderate specificity of the early detection of SARS-CoV-2 IgA antibodies against spike antigens. Either the analysis of antibodies targeting the nucleocapsid antigen or a combination of antibodies against the nucleocapsid and spike antigens may strengthen the accuracy of serological evaluation.

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.

A Pseudo Elevation of CEA Caused by Epidemic Hemorrhagic Fever.

BACKGROUND: Heterophilic antibodies (HA) are one of the main substances that interfere with immunology, especially chemiluminescence immunoassay. Non-specific binding, labeling antibodies, bridging to capture antibodies, or labeling antigens can interfere with the detection process, leading to serious discrepancies between the measured results and clinical manifestations, and even delaying clinical diagnosis and treatment. METHODS: This paper is a case of epidemic hemorrhagic fever causing pseudo CEA elevation caused by heterophagy induced antibodies in the body. RESULTS: The patient's CEA detected on the ABBOTT detection platform was 51.1 ng/mL, and on the ROCHE detection platforms it was 4.66 ng/mL, and treated by PEG precipitation it was 45.2 ng/mL, after diluting the sample the CEA was 50.2 ng/mL, meanwhile the patient's platelets were 96 x 109/L and serum creatinine was 188.4 µmol/L, epidemic hemorrhagic fever IgM antibody was positive. CONCLUSIONS: When the test results do not match clinical symptoms, further confirmation is required through additional testing. Patients who use mouse monoclonal antibody preparations for diagnosis or treatment may have human anti-mouse antibodies in their serum, and the test results may falsely increase or decrease.

The evolving management algorithm for the patient with newly diagnosed cold agglutinin disease.

INTRODUCTION: Cold agglutinin disease (CAD) is driven by IgM autoantibodies reactive at <37°C and able to fix complement. The activation of the classical complement pathway leads to C3-mediated extravascular hemolysis in the liver and to intravascular hemolytic crises in case of complement amplifying conditions. C3 positivity at direct Coombs test along with high titer agglutins are required for the diagnosis. Treatment is less standardized. AREAS COVERED: This review recapitulates CAD diagnosis and then focus on the evolving management of the disease. Both current approach and novel targeted drugs are discussed. Literature search was conducted in PubMed and Scopus from 2000 to 2024 using 'CAD' and 'autoimmune hemolytic anemia' as keywords. EXPERT OPINION: Rituximab represents the frontline approach in patients with symptomatic anemia or disabling cold-induced peripheral symptoms and is effective in 50-60% of cases. Refractory/relapsing patients are an unmet need and may now benefit from complement inhibitors, particularly the anti-C1s sutimlimab, effective in controlling hemolysis thus improving anemia in >80% of patients, but not active on cold-induced peripheral symptoms. Novel drugs include long-acting complement inhibitors, plasma cells, and B-cell targeting agents (proteasome inhibitors, anti-CD38, BTKi, PI3Ki, anti-BAFF). Combination therapy may be the future answer to CAD unmet needs.

Anti-pig antibodies in swine veterinarian serum: Implications for clinical xenotransplantation.

Recent clinical xenotransplantation and human decedent studies demonstrate that clinical hyperacute rejection of genetically engineered porcine organs can be reliably avoided but that antibody mediated rejection (AMR) continues to limit graft survival. We previously identified porcine glycans and proteins which are immunogenic after cardiac xenotransplantation in non-human primates, but the clinical immune response to antigens present in glycan depleted triple knockout (TKO) donor pigs is poorly understood. In this study we use fluorescence barcoded human embryonic kidney cells (HEK) and HEK cell lines expressing porcine glycans (Gal and SDa) or proteins (tetraspanin-29 [CD9], membrane cofactor protein [CD46], protectin, membrane attack complex inhibition factor [CD59], endothelial cell protein C receptor, and Annexin A2) to screen antibody reactivity in human serum from 160 swine veterinarians, a serum source with potential occupational immune challenge from porcine tissues and pathogens. High levels of anti-Gal IgM were present in all samples and lower levels of anti-SDa IgM were present in 41% of samples. IgM binding to porcine proteins, primarily CD9 and CD46, previously identified as immunogenic in pig to non-human primate cardiac xenograft recipients, was detected in 28 of the 160 swine veterinarian samples. These results suggest that barcoded HEK cell lines expressing porcine protein antigens can be useful for screening human patient serum. A comprehensive analysis of sera from clinical xenotransplant recipients to define a panel of commonly immunogenic porcine antigens will likely be necessary to establish an array of porcine non-Gal antigens for effective monitoring of patient immune responses and allow earlier therapies to reverse AMR.

Titers of IgG and IgA against SARS-CoV-2 proteins and their association with symptoms in mild COVID-19 infection.

Humoral immunity in COVID-19 includes antibodies (Abs) targeting spike (S) and nucleocapsid (N) SARS-CoV-2 proteins. Antibody levels are known to correlate with disease severity, but titers are poorly reported in mild or asymptomatic cases. Here, we analyzed the titers of IgA and IgG against SARS-CoV-2 proteins in samples from 200 unvaccinated Hospital Workers (HWs) with mild COVID-19 at two time points after infection. We analyzed the relationship between Ab titers and patient characteristics, clinical features, and evolution over time. Significant differences in IgG and IgA titers against N, S1 and S2 proteins were found when samples were segregated according to time T1 after infection, seroprevalence at T1, sex and age of HWs and symptoms at infection. We found that IgM + samples had higher titers of IgG against N antigen and IgA against S1 and S2 antigens than IgM - samples. There were significant correlations between anti-S1 and S2 Abs. Interestingly, IgM + patients with dyspnea had lower titers of IgG and IgA against N, S1 and S2 than those without dyspnea. Comparing T1 and T2, we found that IgA against N, S1 and S2 but only IgG against certain Ag decreased significantly. In conclusion, an association was established between Ab titers and the development of infection symptoms.

High SARS-CoV-2 infection rate in children unvaccinated with COVID-19 vaccine in Changzhou, China, shortly after lifting zero-COVID-19 policy in December 2022.

BACKGROUND: China experienced an overwhelming COVID-19 pandemic from middle December 2022 to middle January 2023 after lifting the zero-COVID-19 policy on December 7, 2022. However, the infection rate was less studied. We aimed to investigate the SARS-CoV-2 infection rate in children shortly after discontinuation of the zero-COVID-19 policy. METHODS: From February 20 to April 10, 2023, we included 393 children aged 8 months to less than 3 years who did not receive COVID-19 vaccination and 114 children aged 3 to 6 years who received inactivated COVID-19 vaccines based on the convenience sampling in this cross-sectional study. IgG and IgM antibodies against nucleocapsid (N) and subunit 1 of spike (S1) of SARS-CoV-2 (anti-N/S1) were measured with commercial kits (Shenzhen YHLO Biotech, China). RESULTS: Of the 393 unvaccinated children (1.5 ± 0.6 years; 52.2% boys), 369 (93.9%) were anti-N/S1 IgG positive. Of the 114 vaccinated children (5.3 ± 0.9 years; 48.2% boys), 112 (98.2%) were anti-N/S1 IgG positive. None of the unvaccinated or vaccinated children was anti-N/S1 IgM positive. The median IgG antibody titers in vaccinated children (344.91 AU/mL) were significantly higher than that in unvaccinated children (42.80 AU/mL) (P < 0.0001). The positive rates and titers of anti-N/S1 IgG had no significant difference between boys and girls respectively. CONCLUSION: Vast majority of children were infected with SARS-CoV-2 shortly after ending zero-COVID-19 policy in China. Whether these unvaccinated infected children should receive COVID-19 vaccine merits further investigation.

In silico study to explore the mechanism of Toxoplasma-induced inflammation and target therapy based on sero and salivary Toxoplasma.

We aimed to assess salivary and seroprevalence of Toxoplasma immunoglobulins in risky populations and evaluate drug docking targeting TgERP. A cross-sectional study was conducted in Alexandria University hospitals' outpatient clinics. 192 participants were enrolled from September 2022 to November 2023. Anti-Toxoplasma IgG and IgM were determined in serum and saliva by ELISA. An in-Silico study examined TgERP's protein-protein interactions (PPIs) with pro-inflammatory cytokine receptors, anti-inflammatory cytokine, cell cycle progression regulatory proteins, a proliferation marker, and nuclear envelope integrity-related protein Lamin B1. Our findings revealed that anti-T. gondii IgG were detected in serum (66.1%) and saliva (54.7%), with 2.1% of both samples were positive for IgM. Salivary IgG had 75.59% sensitivity, 86.15% specificity, 91.40% PPV, 64.40% NPP, 79.17% accuracy and fair agreement with serum IgG. On the other hand, the sensitivity, specificity, PPV, NPV, and accuracy in detecting salivary IgM were 75.0%, 99.47%, 75.0%, 99.47%, and 98.96%. AUC 0.859 indicates good discriminatory power. Examined synthetic drugs and natural products can target specific amino acids residues of TgERP that lie at the same binding interface with LB1 and Ki67, subsequently, hindering their interaction. Hence, salivary samples can be a promising diagnostic approach. The studied drugs can counteract the pro-inflammatory action of TgERP.

Clinical and historical infection of Tacheng tick virus 2: A retrospective investigation.

BACKGROUND: Tacheng tick virus 2 (TcTV-2) is an emerging tick-borne virus belonging to the genus Uukuvirus in the family Phenuiviridae. Initially isolated in 2019 from a patient in Xinjiang Uygur Autonomous Region (XUAR), northwestern China, who developed fever and headache after a tick bite, TcTV-2 was concurrently molecularly detected in hard ticks across various countries, including China, Kazakhstan, Romania, and Turkey. This study conducted a retrospective epidemiological investigation of TcTV-2 infection. METHODOLOGY: In this retrospective cohort study, we collected samples from 47 tick-bitten patients, 984 herdsmen, 7 Asian badgers, 13 red foxes, and 168 Hyalomma asiaticum tick egg batches. Patients' samples were primarily analyzed by using high-throughput sequencing, targeting the V3-V4 region of the bacterial 16S rRNA gene and viral cDNA libraries. Typical tick-borne pathogens were further confirmed using RT-PCR and detected in Asian badgers, red foxes and Hy. asiaticum tick egg batches. We also conducted enzyme-linked immunosorbent assay (ELISA) to detected specific IgM and IgG antibodies against TcTV-2 in herdsmen. Phylogenetic analysis was performed to genetically characterize TcTV-2 detected in this study. PRINCIPAL FINDINGS: TcTV-2 was detected in various samples, including blood, urine, and throat swabs from 12.77% (6/47) tick-bitten patients. It was found in blood samples of 14.29% (1/7) of wild badgers, 7.69% (1/13) of red foxes, and 13.69% (23/168) of Hy. asiaticum egg batches. Furthermore, ELISA results revealed that 9.55% (94/984) of the serum samples (34 from males and 60 from females) were tested positive for TcTV-2-specific IgG, while 2.95% (29/984, 7 males and 22 females) showed positivity for TcTV-2-specific IgM. Additionally, 1.02% (10/984, 4 males and 6 females) of the sera tested positive for both TcTV-2-specific IgM and IgG. Phylogenetic analysis indicated that the TcTV-2 strains detected in this study were genetically similar, regardless of their origin and host species. CONCLUSIONS: Clinical symptoms of TcTV-2 infection in patients are nonspecific, with common symptoms including headache, fever, asthenia, vomiting, myalgia, rash, and meningitis-like signs. TcTV-2 can be detected in blood, urine, and throat swab samples of infected patients. Among local herdsmen, 9.55% tested positive for TcTV-2-specific IgG and 2.95% for TcTV-2-specific IgM. Importantly, TcTV-2 can be transovarially transmitted in Hy. asiaticum ticks, and the Asian badgers and red foxes are potential reservoirs of TcTV-2.

An unusual outbreak of parvovirus B19 infections, France, 2023 to 2024.

From April 2023 to May 2024, an unusual epidemic of parvovirus B19 (B19V) infections occurred in France. The number of B19V IgM-positive serologies was four times higher than in the previous epidemic in 2019. Clinical data from emergency networks corroborated this observation. Morbidity and mortality consequences were observed in children through all data sources. In adults, the increase was only observed in laboratory-confirmed data. Physicians and decisionmakers should be informed in order to better prevent, diagnose and manage at-risk patients.

High SARS-CoV-2 Exposure in Rural Southern Mozambique After Four Waves of COVID-19: Community-Based Seroepidemiological Surveys.

BACKGROUND: Mozambique was one of many African countries with limited testing capacity for SARS-CoV-2. Serosurveys, an alternative to estimate the real exposure to understand the epidemiology and transmission dynamics, have been scarce in Mozambique. Herein, we aimed to estimate the age-specific seroprevalence of SARS-CoV-2 in the general population of the Manhiça District, at four time points, for evaluating dynamics of exposure and the impact of vaccination. METHODS: We conducted four community-based seroepidemiological surveys separated by 3 months between May 2021 and June 2022 to assess the prevalence of SARS-CoV-2 antibodies. An age-stratified (0-19, 20-39, 40-59, and ≥ 60 years) sample of 4810 individuals was randomly selected from demographic surveillance database, and their blood samples were analyzed using WANTAI SARS-CoV-2 IgG + IgM ELISA. Nasopharyngeal swabs from a subsample of 2209 participants were also assessed for active infection by RT-qPCR. RESULTS: SARS-CoV-2 seroprevalence increased from 27.6% in the first survey (May 2021) to 63.6%, 91.2%, and 91.1% in the second (October 2021), third (January 2022), and fourth (May 2022) surveys, respectively. Seroprevalence in individuals < 18 years, who were not eligible for vaccination, increased from 23.1% in the first survey to 87.1% in the fourth. The prevalence of active infection was below 10.1% in all surveys. CONCLUSIONS: A high seroprevalence to SARS-CoV-2 was observed in the study population, including individuals not eligible for vaccination at that time, particularly after circulation of the highly transmissible Delta variant. These data are important to inform decision making on the vaccination strategies in the context of pandemic slowdown in Mozambique.

The role of immunoglobulin in cerebrospinal fluid on the differential diagnosis of autoimmune encephalitis and viral encephalitis in children.

BACKGROUND: A case-control study was conducted to analyze the role of cerebrospinal fluid immunoglobulin in the differential diagnosis of autoimmune encephalitis and viral encephalitis in children. METHODS: One hundred and twenty patients with autoimmune encephalitis (AE) treated in our hospital from February 2021 to February 2022 were included as the observation group (AE group). 100 patients with viral encephalitis (VE group) were selected as the control group. The clinical data of all patients were collected and analyzed retrospectively. Immunoglobulin G (IgG) and immunoglobulin A (IgA)in cerebrospinal fluid of the two patients were measured by immune turbidimetry. Immunoglobulin M (IgM), and the diagnostic value of immunoglobulin in cerebrospinal fluid (CSF) in patients with AE was analyzed by receiver working curve (ROC). RESULTS: The level of IgG in the cerebrospinal fluid of the AE group was higher than that of the VE group, and the level of IgM was lower than that of the VE group, and the difference was statistically significant (P < 0.05). There was no significant difference in IgA levels between the two groups (P > 0.05). In terms of Magnetic Resonance (MR) features, the paraventricular, hippocampal, occipital and parietal lobes were more involved in AE patients, frontal and temporal lobes were more involved in VE patients, and paraventricular and occipital lobes were involved in MS. The proportion of bilateral extensive lesions in both groups was significantly higher than 50%. The proportions of patients in the AE group involving the lateral ventricle, insula, and parietal lobes were significantly higher than those in the VE group, and the proportions involving the basal ganglia, temporal lobes, and frontal lobes were significantly lower than those in the VE group, and the differences were statistically significant (All P < 0.05). The Area Under Curve (AUC) of IgG, IgA and IgM alone in the diagnosis of AE were 0.795(0.587-0.762), 0.602(0.502-0.631) and 0.627(0.534-0.708), respectively with the sensitivity values of 81.24% and 65.608, respectively and the specificity values of 65.08%, 57.54% and 75.01% respectively. The AUC of IgA + IgM in the diagnosis of AE was 0.733(0.617-0.849), and the sensitivity and specificity are 62.58% and 75.07% respectively. The AUC of IgA + IgG in the diagnosis of AE was 0.823(0.730-0.917), and the sensitivity and specificity were 81.24% and 67.54% respectively. The AUC of IgG + IgM in the diagnosis of AE was 0.886(0.814 ~ 0.958), and the sensitivity and specificity were 84.48% and 77.59% respectively. The AUC of IgA + IgM + IgG in the diagnosis of AE was 0.924 (0.868-0.981) with the sensitivity of 93.82%, and the specificity of 77.56%. CONCLUSION: The level of immunoglobulin in cerebrospinal fluid can be used as an effective reference index for the diagnosis of AE. The combined detection of IgA, IgM and IgG can improve the accuracy, sensitivity and specificity of AE.

Protective efficiency and immune responses to single and booster doses of formalin-inactivated scale drop disease virus (SDDV) vaccine in Asian seabass (Lates calcarifer).

BACKGROUND: Scale drop disease virus (SDDV) threatens Asian seabass (Lates calcarifer) aquaculture production by causing scale drop disease (SDD) in Asian seabass. Research on the development of SDDV vaccines is missing an in-depth examination of long-term immunity and the immune reactions it provokes. This study investigated the long-term immune protection and responses elicited by an SDDV vaccine. The research evaluated the effectiveness of a formalin-inactivated SDDV vaccine (SDDV-FIV) using both prime and prime-booster vaccination strategies in Asian seabass. Three groups were used: control (unvaccinated), single-vaccination (prime only), and booster (prime and booster). SDDV-FIV was administered via intraperitoneal route, with a booster dose given 28 days post-initial vaccination. RESULTS: The immune responses in vaccinated fish (single and booster groups) showed that SDDV-FIV triggered both SDDV-specific IgM and total IgM production. SDDV-specific IgM levels were evident until 28 days post-vaccination (dpv) in the single vaccination group, while an elevated antibody response was maintained in the booster group until 70 dpv. The expression of immune-related genes (dcst, mhc2a1, cd4, ighm, cd8, il8, ifng, and mx) in the head kidney and peripheral blood lymphocytes (PBLs) of vaccinated and challenged fish were significantly upregulated within 1-3 dpv and post-SDDV challenge. Fish were challenged with SDDV at 42 dpv (challenge 1) and 70 dpv (challenge 2). In the first challenge, the group that received booster vaccinations demonstrated notably higher survival rates than the control group (60% versus 20%, P < 0.05). However, in the second challenge, while there was an observable trend towards improved survival rates for the booster group compared to controls (42% versus 25%), these differences did not reach statistical significance (P > 0.05). These findings suggest that the SDDV-FIV vaccine effectively stimulates both humoral and cellular immune responses against SDDV. Booster vaccination enhances this response and improves survival rates up to 42 dpv. CONCLUSIONS: This research provides valuable insights into the development of efficient SDDV vaccines and aids in advancing strategies for immune modulation to enhance disease management in the aquaculture of Asian seabass.

Malaria and other infections induce polyreactive antibodies that impact SARS-CoV-2 seropositivity estimations in endemic settings.

Anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence is used to estimate the proportion of individuals within a population previously infected, to track viral transmission, and to monitor naturally and vaccine-induced immune protection. However, in sub-Saharan African settings, antibodies induced by higher exposure to pathogens may increase unspecific seroreactivity to SARS-CoV-2 antigens, resulting in false positive responses. To investigate the level and type of unspecific seroreactivitiy to SARS-CoV-2 in Africa, we measured immunoglobulin G (IgG), IgA, and IgM to a broad panel of antigens from different pathogens by Luminex in 602 plasma samples from African and European subjects differing in coronavirus disease 2019, malaria, and other exposures. Seroreactivity to SARS-CoV-2 antigens was higher in prepandemic African than in European samples and positively correlated with antibodies against human coronaviruses, helminths, protozoa, and especially Plasmodium falciparum. African subjects presented higher levels of autoantibodies, a surrogate of polyreactivity, which correlated with P. falciparum and SARS-CoV-2 antibodies. Finally, we found an improved sensitivity in the IgG assay in African samples when using urea as a chaotropic agent. In conclusion, our data suggest that polyreactive antibodies induced mostly by malaria are important mediators of the unspecific anti-SARS-CoV-2 responses, and that the use of dissociating agents in immunoassays could be useful for more accurate estimates of SARS-CoV-2 seroprevalence in African settings.

Geographic heterogeneity of SARS-CoV-2 circulation in Abidjan, Ivory Coast: a prospective study.

INTRODUCTION: Few studies on SARS-CoV-2 seroprevalence in Ivory Coast have been conducted since the first case was reported on March 11, 2020. The main objective of this study was to observe and better understand the circulation of SARS-CoV-2 in Abidjan. METHODOLOGY: This prospective study collected data concerning age, sex, vaccination status, municipality of origin, monthly income, frequency of malaria, and frequency of diarrheal diseases in persons who gave their informed consent. Venous blood samples were taken to test for anti-SARS-COV-2 antibodies (IgM and IgG) using the VIDAS automated system. RESULTS: A total of 1504 patients were recruited and tested for antibodies directed against SARS-COV-2. Data analysis revealed the presence of anti-SARS-CoV-2 in 53.5% of participants, 17.3% of the participants had a previous symptomatic infection, 31.4% had an asymptomatic infection, and 44.8% were never in contact with the virus. Seroprevalence of SARS-CoV-2 was higher in Marcory (70.9%) and Cocody (61.1%) than in the remaining townships (48.4%). Township rates of serologically confirmed SARS-CoV-2 infection correlated with poverty index (p = 0.025), children < 5 years' proportion in the township (p = 0.026), and levels of malaria (p = 0.034). CONCLUSIONS: In the city of Abidjan, COVID-19 is strongly modulated by poverty, the proportion of babies and toddlers in the community, or exposure to malaria.

Novel paradigm enables accurate monthly gestational screening to prevent congenital toxoplasmosis and more.

BACKGROUND: Congenital toxoplasmosis is a treatable, preventable disease, but untreated causes death, prematurity, loss of sight, cognition and motor function, and substantial costs worldwide. OBJECTIVES: We asked whether high performance of an Immunochromatographic-test (ICT) could enable accurate, rapid diagnosis/treatment, establishing new, improved care-paradigms at point-of-care and clinical laboratory. METHODS: Data were obtained in 12 studies/analyses addressing: 1-feasibility/efficacy; 2-false-positives; 3-acceptability; 4-pink/black-line/all studies; 5-time/cost; 6-Quick-Information/Limit-of-detection; 7, 8-acute;-chronic; 9-epidemiology; 10-ADBio; 11,12-Commentary/Cases/Chronology. FINDINGS: ICT was compared with gold-standard or predicate-tests. Overall, ICT performance for 1093 blood/4967 sera was 99.2%/97.5% sensitive and 99.0%/99.7% specific. However, in clinical trial, FDA-cleared-predicate tests initially caused practical, costly problems due to false-positive-IgM results. For 58 persons, 3/43 seronegative and 2/15 chronically infected persons had false positive IgM predicate tests. This caused substantial anxiety, concerns, and required costly, delayed confirmation in reference centers. Absence of false positive ICT results contributes to solutions: Lyon and Paris France and USA Reference laboratories frequently receive sera with erroneously positive local laboratory IgM results impeding patient care. Therefore, thirty-two such sera referred to Lyon's Reference laboratory were ICT-tested. We collated these with other earlier/ongoing results: 132 of 137 USA or French persons had false-positive local laboratory IgM results identified correctly as negative by ICT. Five false positive ICT results in Tunisia and Marseille, France, emphasize need to confirm positive ICT results with Sabin-Feldman-Dye-test or western blot. Separate studies demonstrated high performance in detecting acute infections, meeting FDA, CLIA, WHO REASSURED, CEMark criteria and patient and physician satisfaction with monthly-gestational-ICT-screening. CONCLUSIONS/SIGNIFICANCE: This novel paradigm using ICT identifies likely false positives or raises suspicion that a result is truly positive, rapidly needing prompt follow up and treatment. Thus, ICT enables well-accepted gestational screening programs that facilitate rapid treatment saving lives, sight, cognition and motor function. This reduces anxiety, delays, work, and cost at point-of-care and clinical laboratories. TRIAL REGISTRATION: NCT04474132, https://clinicaltrials.gov/study/NCT04474132 ClinicalTrials.gov.

Seroprevalence of Japanese encephalitis virus in pig populations of Tamil Nadu, India: Exploring the tropical endemic link of virus.

Japanese encephalitis virus (JEV) is a major cause of encephalitis in Southeast Asia. Tamil Nadu, a state located in the southern part of India, contributes substantially to the national burden of human JE cases every year. However, limited information is available on the epidemiology of JE in pig populations of Tamil Nadu. A cross-sectional study was conducted to assess JEV prevalence in pig populations of Tamil Nadu. A total of 710 pigs reared in 118 farms across 10 districts of Tamil Nadu were sampled using multistage cluster random sampling. Serum samples were analyzed for their JEV status using Immunoglobulin M (IgM) and Immunoglobulin G (IgG) Enzyme-Linked Immunosorbent Assay (ELISA). At the animal-level, the apparent JEV seroprevalence was 60.4% (95% CI: 56.8% - 64.0%) and the true seroprevalence was 50.1% (95% CI: 47.0% - 53.2%). The herd-level apparent seroprevalence was 94.1% (95% CI: 88.1% - 97.5%) and the true seroprevalence was 93.3% (95% CI: 89.5% - 96.2%). The intensity of JEV circulation was high in all the districts, with seroprevalence ranging between 43% and 100%. Pigs across all age categories were seropositive and a high overall seroprevalence of 95.2% (95% CI: 76.2% - 99.9%) was recorded in pigs older than 12 months. JEV seropositivity was recorded in all the seasons but the prevalence peaked in the monsoon (67.9%, 95% CI: 61.1% - 74.2%) followed by winter (65.1%, 95%CI: 57.4% - 72.2%) and summer (53.3%, 95% CI: 47.8% - 58.8%) seasons. The results indicate that JEV is endemic in pigs populations of the state and a one health approach is essential with collaborative actions from animal and public health authorities to control JE in Tamil Nadu, India.

Rational design and production of a chimeric antigen targeting Zika virus that induces neutralizing antibodies in mice.

The Zika virus (ZIKV) is considered a public health problem worldwide due to its association with the development of microcephaly and the Guillain-Barré syndrome. Currently, there is no specific treatment or vaccine approved to combat this disease, and thus, developing safe and effective vaccines is a relevant goal. In this study, a multi-epitope protein called rpZDIII was designed based on a series of ZIKV antigenic sequences, a bacterial carrier, and linkers. The analysis of the predicted 3D structure of the rpZDIII chimeric antigen was performed on the AlphaFold 2 server, and it was produced in E. coli and purified from inclusion bodies, followed by solubilization and refolding processes. The yield achieved for rpZDIII was 11 mg/L in terms of pure soluble recombinant protein per liter of fermentation. rpZDIII was deemed immunogenic since it induced serum IgG and IgM responses in mice upon subcutaneous immunization in a three-dose scheme. Moreover, sera from mice immunized with rpZDIII showed neutralizing activity against ZIKV. Therefore, this study reveals rpZDIII as a promising immunogen for the development of a rationally designed multi-epitope vaccine against ZIKV, and completion of its preclinical evaluation is guaranteed.