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Chagas disease is a chronic parasitological disease, which could cause cardiac manifestations in approximately one-third of affected individuals. Benznidazole and nifurtimox are used to treat this parasitological infection caused by Trypanosoma cruzi. Conventionally, the criterion for cure is consistently negative serological tests after treatment. We report a case of a patient who was treated when she was 13 years old and achieved T. cruzi negative seroconversion but developed Chagas disease cardiomyopathy as an adult.

Objective: This study aimed to discuss adjusting the treatment plan for patients with type 2 diabetes mellitus (T2DM) who are positive for exogenous insulin antibody (IA). The outcome of patients who are IA-positive with an adjusted treatment plan was considered. Methods: The treatment plan for patients with IA-positive T2DM was adjusted to oral medication or long-acting insulin + oral medication. Insulin antibody, C-peptide, and insulin were re-examined before treatment and at 1, 3, 6, 12, 18, and 24 months after treatment. The time of IA-negative seroconversion and its indexes, including blood glucose, C-peptide, and insulin, were recorded and analyzed. Results: After adjusting the treatment plan for 2 years, in 73 patients, 57 had IA-negative seroconversion, and 16 had positive IA. The blood glucose, C-peptide, insulin, glycosylated hemoglobin (HbA1c), and the daily dose of insulin in the seroconversion group and the non-seroconversion group decreased compared with before the adjustment of the treatment plan (P < 0.05). The negative seroconversion rate within 2 years was related to the insulin concentration before treatment. Conclusion: Patients with IA-positive T2DM need to adjust their treatment plans in time. Even if IA does not turn negative within 2 years after adjusting the treatment plan, the levels of blood glucose, C-peptide, insulin, and HbA1c along with the insulin dosage would be significantly improved, which can benefit patients. The higher the fasting insulin and 2-hour insulin values before adjusting the treatment plan, the longer the time required for IA to turn negative. Keywords: insulin antibody, diabetes, type 2, negative seroconversion rate

ObjectiveAlthough most patients with chronic hepatitis B (CHB) reach effective virological suppression with long-term nucleos(t)ide analogues (NA) therapy, some might not need to continue treatment for life. In this randomised, controlled, phase IV trial, we evaluated off-therapy outcomes in patients after discontinuing long-term NA therapy.DesignPatients who had received NA therapy for ≥1 year and achieved virological suppression (hepatitis B e antigen (HBeAg) seroconversion combined with undetectable hepatitis B virus (HBV) DNA ≥12 months in HBeAg-positive patients or undetectable HBV DNA ≥36 months in HBeAg-negative patients) were randomised 2:1 to stop or continue NA therapy for 72 weeks. Sustained disease remission (HBeAg negative, HBV DNA <2000 IU/mL and normal alanine aminotransferase (ALT)) was evaluated at 72 weeks after stopping NA therapy.ResultsAmong 67 enrolled patients, sustained disease remission was observed in 13/45 (29%) stop versus 18/22 (82%) continue patients. Hepatitis B surface antigen (HBsAg) loss occurred in two patients (one in each group). The median HBsAg decline from randomisation to week 72 was similar in both groups (0.2 (0.0–0.4) vs 0.1 (0.0–0.2) log IU/mL in stop vs continue patients). Among patients who stopped, 15/45 (33%) had virological or biochemical relapse and 17/45 (38%) were retreated according to predefined criteria. A total of 11/18 (61%) pretreatment HBeAg-positive versus 6/27 (22%) HBeAg-negative patients required retreatment (p=0.01). Fourteen (31%) patients developed ALT >10× upper limit of normal (ULN) and another 7 (16%) had ALT >5× ULN. No patients experienced liver decompensation or died.ConclusionThe findings of this prospective study suggest limited benefit of stopping NA therapy in chronic hepatitis B.Trial registration number NCT01911156.

The immunopathogenesis of chronic hepatitis B (CHB) with unclear immune phases hinders functional cure. For highly infectious HBeAg-positive (HBeAg + ) patients where functional cure is unattainable, achieving sustained HBeAg seroconversion constitutes the key therapeutic objective. This study used single-cell sequencing (scRNA-seq) to analyze B-cell subsets dynamics during HBeAg seroconversion and their roles in restricting HBsAg seroconversion. ScRNA-seq datasets (GSE182159, GSE234241) were retrieved from the GEO database, comprising 67 peripheral blood/liver samples. After batch correction and integration, compared with the two HBeAg + phases, patients with HBeAg-negative (HBeAg⁻) chronic HBV infection show opposite distribution trends of naive and memory B cells in peripheral blood and liver. Compared with healthy controls and chronic resolved (CR) cases, the HBeAg⁻ chronic HBV infection and HBeAg⁻ groups showed decreased plasma cell proportions in both peripheral blood and liver along with increased hepatic non-switched and switched memory B cells. Functional analysis indicates that B cell subsets in the HBeAg + group may present more severe metabolic dysfunctions, epigenetic abnormalities, as well as signaling and differentiation defects compared to the HBeAg⁻ group, suggesting a potential pivotal role of B cell subsets in HBeAg seroconversion. Moreover, relative to the CR group, B cell subsets in the HBeAg⁻ group are likely to exhibit more profound energy metabolic impairment and aberrant immune activation, which may consequently facilitate the persistence of HBV infection. B-cell subsets may play a pivotal role in HBeAg seroconversion, and their altered proportions and functional defects may further contribute to the persistence of HBV infection.

Objective:To assess risk factors for liver-related death, we re-evaluated, after a median follow-up of 25 years, a cohort of 70 Caucasian patients with hepatitis B e antigen (HBeAg) positive chronic hepatitis (CH) at presentation.Methods:Follow-up studies included clinical and ultrasound examinations, biochemical and virological tests, and cause of death.Results:Sixty-one (87%) patients underwent spontaneous HBeAg seroconversion. During a median period of 22.8 years after HBeAg seroclearance, 40 (66%) patients became inactive carriers, whereas the remaining 21 (34%) showed alanine aminotransferase elevation: one (1%) had HBeAg reversion, nine (15%) detectable serum HBV DNA but were negative for HBeAg, eight (13%) concurrent virus(es) infection and three (5%) concurrent non-alcoholic fatty liver disease. Liver-related death occurred in 11 (15.7%) patients, caused by hepatocellular carcinoma in five and liver failure in six. The 25-year survival probability was 40% in patients persistently HBeAg positive, 50% in patients with HBeAg negative CH or HBeAg reversion and 95% in inactive carriers. Older age, male sex, cirrhosis at entry and absence of sustained remission predicted liver-related death independently. The adjusted hazard ratios (95% CI) for liver related death were 33 (3.01–363) for persistently HBeAg positive patients and 38.73 (4.65–322) for those with HBeAg negative CH or HBeAg reversion relative to inactive carriers.Conclusion:Most patients with HBeAg seroconversion became inactive carriers with very good prognosis. The risk of liver-related mortality in Caucasian adults with CH is strongly related with sustained disease activity and ongoing high level of HBV replication independently of HBeAg status.

Tularemia is caused by Francisella tularensis, a gram-negative bacterium that has been weaponized as an aerosol. For protection of personnel conducting biodefense research, the United States Army required clinical evaluation of a new lot of tularemia live vaccine strain manufactured in accordance with Current Good Manufacturing Practices. A phase 2 randomized clinical trial compared the new lot (DVC-LVS) to the existing vaccine that has been in use for decades (USAMRIID-LVS). The vaccines were delivered by scarification to 228 participants. Safety, reactogenicity, take and/or antibody levels were assessed on days 0, 1, 2, 8, 14, 28, 56, and 180. Both vaccines were safe and had acceptable reactogenicity profiles during six months of follow-up. There were no serious or grade 3 and 4 laboratory adverse events. Moderate systemic reactogenicity (mostly headache or feeling tired) was reported by ∼23% of participants receiving either vaccine. Injection site reactogenicity was mostly mild itchiness and pain. The frequencies of vaccine take skin reactions were 73% (95% CI, 64, 81) for DVC-LVS and 80% (95% CI, 71, 87) for USAMRIID-LVS. The 90% CI for the difference in proportions was −6.9% (−16.4, 2.6). The rates of seroconversion measured by microagglutination assay on days 28 or 56 were 94% (95% CI, 88, 98; n=98/104) for DVC-LVS and 94% (95% CI, 87, 97; n=103/110) for USAMRIID-LVS (p=1.00). Day 14 sera revealed more rapid seroconversion for DVC-LVS relative to USAMRIID-LVS: 82% (95% CI, 73, 89) versus 55% (95% CI, 45, 65), respectively (p<0.0001). The DVC-LVS vaccine had similar safety, reactogenicity, take and antibody responses compared to the older USAMRIID vaccine, and was superior for early (day 14) antibody production. Vaccination take was not a sensitive surrogate for seroconversion in a multi-center study where personnel at five research clinics performed assessments. ClinicalTrials.gov identifier NCT01150695

Bordetella pertussis , a gram-negative bacterium responsible for whooping cough, poses severe health risks, especially to young children. However, the disease can be prevented by immunization with whole-cell pertussis vaccines and acellular pertussis vaccines containing 2–5 purified B. pertussis antigens, of which chemically detoxified pertussis toxin is the main protective component. While current vaccines have proven effective, concerns over high reactogenicity of whole-cell pertussis vaccines and the waning immunity to acellular pertussis vaccines formulations underscore the need for improved pertussis vaccines. Genetically detoxified pertussis toxin is an attractive vaccine candidate because it retains most of the structural properties of native pertussis toxin and better preserves the protective epitopes compared to detoxified pertussis toxin. In this study, we developed a candidate vaccine based on a genetically detoxified pertussis toxin S1 subunit, gd15PTxS1. We evaluated humoral and cellular immunogenicity of gd15PTxS1 in a murine model and demonstrated significant anti-PTx IgG seroconversion and a balanced Th1/Th2/Th17 T-cell response, with gd15PTxS1 inducing robust cytotoxic and helper T-cell activation comparable to that of the whole-cell pertussis vaccines. Our results show that gd15PTxS1 is highly immunogenic in mice and is a promising vaccine candidate for further protectivity studies.

Hepatitis B virus (HBV) infection is a major public health problem worldwide. The study aimed to evaluate the efficacy of pegylated interferon (Peg-IFN) alfa-2a treatment for seroclearance of HBs antigen (HBsAg) in HBe antigen (HBeAg)-negative chronic hepatitis B (CHB) patients. This retrospective study investigated 16 HBeAg-negative CHB patients who received Peg-IFN alfa-2a weekly for 48 weeks. Thereafter, the patients were followed-up for 48 weeks after the end of therapy. The following criteria were also used for inclusion: HBV-DNA < 5.0 log copies/mL and without nucleot(s)ide analogs. Four HBsAg-positive cases became HBsAg negative. The HBsAg levels of the 4 patients who achieved HBsAg seroclearance were lower significantly than that of the non-seroclearance group (p = 0.007). The mean HBsAg levels in these 4 cases were 68 IU/mL, while the mean HBsAg levels in the non-seroclearance group were 2,114 IU/mL. The mean HBV-DNA levels in the 4 HBsAg seroclearance cases were 2.8 log copies/mL as compared to 3.6 log copies/mL in HBsAg-non-seroclearance cases (p = 0.01). Cases that are HBeAg negative, with HBV-DNA levels < 5 log copies/mL, and HBsAg titers < 120 IU/mL cases may achieve HBsAg clearance with Peg-IFN therapy.

We report of two cases of progressed COVID-19 with negative PCR tests from nasopharyngeal swabs, in whom diagnosis was made by different antibody assays, including a lateral flow rapid test and multiple commercial ELISAs, finally confirmed by comprehensive serological assays. These cases highlight that commercial ELISAs and even rapid tests might significantly aid the diagnosis of COVID-19, particularly, if a combination of serological assays is used with a specific clinical question, in severely ill patients after seroconversion and when comprehensive serological methods are used for confirmation.

Background Rabies is a fatal disease that is preventable when post exposure prophylaxis (PEP) is administered in a timely fashion. CpG oligodeoxynucleotides (ODNs) can trigger cells that express Toll-like receptor 9, and their immunopotentiation activity in an inactivated aluminum-adjuvanted rabies vaccine for dogs has been identified using mouse and dog models. Methods A human diploid cell rabies vaccine (HDCV) of humans and a CpG ODNs with cross-immunostimulatory activity in humans and mice were used to evaluate the immunogenicity and protective efficacy of CpG ODN in a mouse model that simulates human PEP. Results HDCV combined with CpG ODN (HDCV–CpG) stimulated mice to produce rabies virus-specific neutralizing antibody (RVNA) earlier and increased the seroconversion rate. Compared with HDCV alone, either HDCV–1.25 μg CpG or HDCV–5 μg CpG increased the levels of RVNA. In particular, 5 μg CpG ODN per mouse significantly boosted the levels of RVNA compared with HDCV alone. IFN-γ producing splenocytes generated in the HDCV-5 μg CpG group were significantly increased compared to the group treated with HDCV alone. When the immunization regimen was reduced to three injections or the dose was reduced to half of the recommended HDCV combined with CpG ODN, the RVNA titers were still higher than those induced by HDCV alone. After viral challenge, 50% of mice immunized with a half-dose HDCV–CpG survived, while the survival rate of mice immunized with HDCV alone was 30%. Conclusions The immunopotentiation activity of CpG ODNs for a commercially available human rabies vaccine was first evaluated in a mouse model on the basis of the Essen regimen. Our results suggest that the CpG ODN used in this study is a potential adjuvant to rabies vaccines for human use.