Primary Toxoplasma gondii infection-associated with hemophagocytic syndrome in a man with HIV infection: a case report

Background Reactivation of latent Toxoplasma gondii (T. gondii) infection is more common than primary infection in patients with human immunodeficiency virus (HIV). We report a rare case of primary T. gondii infection-associated hemophagocytic syndrome (HPS). Case presentation A man with HIV infection presented with fever, dyspnea and pancytopenia. He was diagnosed with primary T. gondii infection by the seroconversion from single-positive IgM antibody to double-positive IgM and IgG antibody. Metagenomic next-generation sequencing (mNGS) of a plasma sample yielded high reads of T. gondii DNA. He responded well to combined anti-Toxoplasma medicines and glucocorticoid treatment. Conclusions In patients with HPS and positive T. gondii IgM antibody, mNGS analysis of a peripheral blood sample is helpful in diagnosing disseminated T. gondii infection. The dynamic changes by serological detection for IgM and IgG of T. gondii further supported the inference that the patient has experienced a primary T. gondii infection.

Capacity of a Multiplex IgM Antibody Capture ELISA to Differentiate Zika and Dengue Virus Infections in Areas of Concurrent Endemic Transmission

Serological cross-reactivity has proved to be a challenge to diagnose Zika virus (ZIKV) infections in dengue virus (DENV) endemic countries. Confirmatory testing of ZIKV IgM positive results by plaque reduction neutralization tests (PRNTs) provides clarification in only a minority of cases because most individuals infected with ZIKV were previously exposed to DENV. The goal of this study was to evaluate the performance of a ZIKV/DENV DUO IgM antibody capture ELISA (MAC-ELISA) for discriminating between DENV and ZIKV infections in endemic regions. Our performance evaluation included acute and convalescent specimens from patients with real-time reverse transcription polymerase chain reaction (RT-PCR)-confirmed DENV or ZIKV from the Sentinel Enhanced Dengue Surveillance System in Ponce, Puerto Rico. The ZIKV/DENV DUO MAC-ELISA specificity was 100% for DENV (N = 127) and 98.4% for ZIKV (N = 275) when specimens were tested during the optimal testing window (days post-onset of illness [DPO] 6–120). The ZIKV/DENV DUO MAC-ELISA sensitivity of RT-PCR confirmed specimens reached 100% for DENV by DPO 6 and for ZIKV by DPO 9. Our new ZIKV/DENV DUO MAC-ELISA was also able to distinguish ZIKV and DENV regardless of previous DENV exposure. We conclude this novel serologic diagnostic assay can accurately discriminate ZIKV and DENV infections. This can potentially be useful considering that the more labor-intensive and expensive PRNT assay may not be an option for confirmatory diagnosis in areas that lack PRNT capacity, but experience circulation of both DENV and ZIKV.

Treatment with IgM-enriched intravenous immunoglobulins (IgM-IVIg) enhances clearance of stroke-associated bacterial lung infection

Post-stroke infection is a common complication of stroke that is associated with increased mortality and morbidity. We previously found that experimental stroke induces an ablation of multiple sub-populations of B cells and reduced levels of IgM antibody that coincide with the development of spontaneous bacterial pneumonia. Reduced circulating IgM concentrations were also observed in acute stroke patients. The loss of IgM antibody after stroke could be an important determinant of infection susceptibility and highlights this pathway as an important target for intervention. We treated mice with a low (replacement), dose of IgM-enriched intravenous immunoglobulin (IgM-IVIg) prior to and 24 h after experimental stroke induced by middle cerebral artery occlusion (MCAO) or sham surgery, then recovered mice for 2 d or 5 d. The effect of treatment on lung bacterial burden, lung pathology, brain infarct volume, antibody levels and both lung and systemic cellular and cytokine immune profiles was determined. Treatment with IgM-IVIg enhanced bacterial clearance from the lung after MCAO and improved pathology but did not impact infarct volume. IgM-IVIg treatment induced immunomodulatory effects systemically including rescue of splenic plasma B cell numbers and endogenous mouse IgM and IgA circulating immunoglobulin concentrations that were reduced by MCAO, and treatment also reduced concentrations of pro-inflammatory cytokines in the lung. The effects of MCAO and IgM-IVIg treatment on the immune system were tissue specific as no impact on B cells or mouse immunoglobulins were found within the lung. However, the presence of human immunoglobulins from the IgM-IVIg treatment led to increased total lung immunoglobulin concentration. IgM-IVIg treatment did not increase the number of lung mononuclear phagocytes or directly modulate macrophage phagocytic capacity but enhanced their capability to phagocytose Staphylococcus aureus bioparticles in vitro by increasing opsonisation. Low dose IgM-IVIg contributes to increased clearance of spontaneous lung bacteria after MCAO likely via increasing availability of antibody in the lung to enhance phagocytic activity. Immunomodulatory effects of IgM-IVIg treatment, including reduced pro-inflammatory cytokine production, may also contribute to reduced levels of damage in the lung after MCAO. IgM-IVIg shows promise as an antibacterial and immunomodulatory agent to use in the treatment of post-stroke infection.

SARS-CoV-2 Seroprevalence and Profiles Among Convalescents in Sichuan Province, China

Objectives: To explore and understand the SARS-CoV-2 seroprevalence of convalescents, the association between antibody levels and demographic factors, and the seroepidemiology of convalescents of COVID-19 till March 2021.Methods: We recruited 517 voluntary COVID-19 convalescents in Sichuan Province and collected 1,707 serum samples till March 2021. Then we reported the seroprevalence and analyzed the associated factors.Results: Recent travel history was associated with IgM levels. Convalescents who had recent travel history were less likely to be IgM antibody negative [OR = 0.232, 95% CI: (0.128, 0.420)]. Asymptomatic cases had, approximately, twice the odds of being IgM antibody negative compared with symptomatic cases [OR = 2.583, 95% CI: (1.554, 4.293)]. Participants without symptoms were less likely to be IgG seronegative than those with symptoms [OR = 0.511, 95% CI: (0.293, 0.891)]. Convalescents aged 40–59 were less likely to be IgG seronegative than those aged below 20 [OR = 0.364, 95% CI: (0.138, 0.959)]. The duration of positive IgM antibodies persisted 365 days while the IgG persisted more than 399 days.Conclusions: Our findings suggested that recent travel history might be associated with the antibody levels of IgM, while age could be associated with the antibody levels of IgG. Infection type could be associated with both antibody levels of IgM and IgG that declined quicker in asymptomatic cases.

Sex Differences in Case Fatality Rate of Patients With Severe Fever With Thrombocytopenia Syndrome

Background: Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne disease with high mortality. However, detailed analysis is lacking to explore the complex effect of sex with age or comorbidities.Methods: A retrospective cohort study was performed among 2,938 SFTS patients entered during 2011–2020 in Xinyang, China. The case fatality rate (CFR) was estimated for their association with sex, age, and comorbidities by an interactive way. The difference of immune response between sex was explored in an age dependent way.Results: An overall CFR of 15.3% (450/2,938) was obtained, which appeared to be higher in males than in females [17.7% vs. 13.6%, adjusted odds ratio (aOR) = 1.24; 95% CI, 1.00–1.53; P = 0.048] and increased dramatically with age (P < 0.001). The associations between sex and SFTS fatal outcome were age-dependent and varied according to the status of comorbidities. The mortality-related risk conferred by older age was more pronounced in males, with aOR (95% CI) to be 5.76 (3.75–8.84) vs. 5.30 (3.54–7.95) in female. Sex-stratified analysis disclosed significant associations between death and comorbidities among female patients (aOR = 1.87, 95% CI: 1.40–2.49; P < 0.001), while none among males. Among females, the significant associations between presence of comorbidity and fatal outcome differed among age groups, with aOR (95% CI) decreased from 2.28 (1.16–4.46) in ≤60 years, to 2.06 (1.34–3.18) in 60–70 years and further to 1.55 (0.97–2.47) in >70 years. Altogether 194 SFTS patients were randomly selected for the test of B cells, natural killer (NK) cells, CD4 cells percentages, and anti-SFTSV IgM antibody level, the results revealed that males >60 years had significantly decreased percentages of B cells, CD4 cells, lower anti-SFTSV IgM antibody titer, and increased level of NK cells than male aged ≤60 years, while none of these age specific differences was observed in the females. This finding underlies the more pronounced age specific difference in CFR among male than female.Conclusions: Males had a significantly higher mortality of SFTS than did females, and more likely to be affected by aging for SFTS mortality. This difference can be explained by the effect from comorbidities and the host immunity. It is essential to take a sex- and age-based approach to SFTS treatment and management.

Detection of NS1 antigen, IgM and IgG antibodies using a commercial Dengue rapid test kit for the diagnosis of dengue infection in patients with acute febrile illness

Dengue is an endemic arboviral illness. With the increasing incidence of dengue infection, an early diagnostic confirmation of dengue infection in patients facilitates timely clinical intervention, etiological investigation, and disease control. Objective of this study was to evaluate a commercially available serological test kit - Dengue Day 1 Test. This is for the detection of dengue NS1 antigen, differential detection of IgM and IgG antibodies on a single acute serum sample. Atotal of 100 patients with acute febrile illness were included in this study. Serum samples were analysed for Dengue NS1 Ag, IgM & IgG Antibodies using a commercially available Dengue Day 1 Test, rapid solid phase immuno-chromatographic test.As many as 23 (23%) samples were NS1 positive and 17 (17%) samples were positive for IgM antibodies. Based on the combination of dengue NS1 antigen and IgM antibody test, total of 34 patients (34%) were positive for dengue virus infection.Results of the study suggested that a combination of dengue NS1 antigen and IgM antibody tests would increase the rate of detection of dengue illness. This combination would increase the efficacy and aid in early diagnosis of dengue infection.

Evaluation of a SARS-CoV-2 Capture IgM Antibody Assay in Convalescent Sera

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has inflicted tremendous loss of lives, overwhelmed health care systems, and disrupted all aspects of life worldwide since its emergence in Wuhan, China, in December 2019. Detecting current and past infection by PCR or serology is important to understanding and controlling SARS-CoV-2.

A high-throughput microsphere-based immunoassay of anti-SARS-CoV-2 IgM testing for COVID-19 diagnostics

The pandemic of novel coronavirus disease COVID-19 is rapidly expanding across the world. A positive result of antibody tests suggests that the individual has potentially been exposed to SARS-CoV-2, thus allowing to identify asymptomatic infections and determine the seroprevalence in a given population. The aim of this study was to evaluate the performances of a newly developed high throughput immunoassay for anti-SARS-CoV-2 IgM antibody detection on the Luminex MAGPIX platform. Clinical agreement studies were performed in 42 COVID-19 patient serum samples and 162 negative donor serum/plasma samples. Positive percent agreement (PPA) was 42.86% (95% CI: 9.90% to 81.59%), 71.43% (95% CI: 29.04% to 96.33%), and 28.57% (95% CI: 13.22% to 48.67%) for samples collected on 0–7 days, 8–14 days, and 2–8 weeks from symptom onset, respectively. Negative Percent Agreement (NPA) was 97.53% (95% CI: 93.80% to 99.32%). There was no cross-reactivity with the SARS-CoV-2 IgG antibody. Hemoglobin (200 mg/dL), bilirubin (2 mg/dL), triglyceride (250 mg/dL) and EDTA (10 mM) showed no significant interfering effect on this assay. In conclusion, an anti-SARS-CoV-2 IgM antibody assay with high sensitivity and specificity has been developed. With the high throughput, this assay will speed up the anti-SARS-CoV-2 IgM testing.