Journal of Infectious Diseases最新文献

Background: Xpert MTB-Host Response (MTB-HR) has reached WHO test targets for pulmonary tuberculosis (PTB) with high bacillary loads. Our aim was to investigate the contribution of MTB-HR as a non-sputum, near point-of-care (POC) method for diagnosis of other prioritized groups, where MTB detection is more complicated, such as extrapulmonary tuberculosis (EPTB) and paucibacillary PTB.

Methods: Individuals with presumed TB disease were prospectively included in Stockholm, Sweden (n=307) and underwent MTB-HR venous and capillary testing in parallel. Clinical characterization was based on symptoms, microbiological results (microscopy, PCR and culture), radiological assessment and a panel of routine biochemical tests. ROC-analysis was performed in PTB and EPTB calculating cut-offs for maximized sensitivity and specificity including WHO targets for screening and diagnostic tests.

Findings: MTB-HR performed equally well in individuals with microbiologically confirmed PTB (AUC 0.84; 95% CI: 0.78-0.90, n=69) and EPTB (AUC 0.82 (95% CI: 0.75-0.90, n=34). Based on Youden index cut-offs the NPV was high both in microscopy- and PCR-negative PTB (-1.27, NPV 94%) and in EPTB (-1.58, NPV 95%) and fulfilled the minimum TPP sensitivity requirement for confirmed EPTB. In individuals without TB (n=204), the majority had pulmonary infectious diseases. There was a close to perfect correlation between venous and capillary samples (r= 0.97, p<0.001).

Interpretation: Capillary Xpert MTB-HR improves detection of sputum PCR-negative, culture-verified PTB and is promising as a rule-out test in EPTB. There was a strong correlation between MTB-HR score and bacterial burden. We suggest a graded MTB-HR score as more clinically relevant than a binary test result.

Background: Primate T-cell leukemia virus type 1 (PTLV-1) is classified into a genus Deltaretrovirus that persists in infected primates and can lead to adult T cell leukemia and inflammatory diseases. Unlike hepatitis viruses, it remains unclear whether PTLV-1 could cause occult infection, a rare latent infection status characterized by detectable provirus without accompanying antibody responses.

Methods: A longitudinal study was conducted to characterize mother-to-child transmission of simian T cell leukemia virus type 1 (STLV-1) in Japanese monkeys (JMs). Stored blood samples obtained from STLV-1-infected JM mothers and their offspring were analyzed for proviral loads, antiviral antibody titers, proviral DNA sequencing, transcriptional capability, and clonality of the infected cells.

Results: One JM infant was found to be positive for proviral DNA without detectable anti-STLV-1 antibodies. The seronegative infection persisted for at least five years, despite positive antibody responses to other viruses that are widespread in JMs. Further analyses of the infant's blood demonstrated that (i) the provirus had no defective mutations, (ii) tax mRNA expression could be induced by in vitro culture, and (iii) substantial numbers of heterogeneous clones of STLV-1-infected cells were undergoing sequential turnover. In an additional retrospective study of a large JMs cohort, three out of 36 offspring of STLV-1-infected mothers were found to be persistently infected with STLV-1 without seroconversion.

Conclusion: Our findings demonstrate that maternal STLV-1 transmission can occasionally persist for years without seroconversion. This represents the first discovery of occult infection in the genus Deltaretrovirus.

Background: The impact of long-acting injectable cabotegravir plus rilpivirine (CAB/RPV) on rectal HIV-1 RNA dynamics and the factors associated with viral shedding remain poorly understood.

Methods: This prospective study evaluated HIV-1 RNA dynamics by analyzing sequential paired plasma and rectal fluid samples from virologically-suppressed individuals who transitioned from oral antiretroviral therapy (ART) to every-two-month CAB/RPV (preceded or not by oral lead-in), over a 9-month follow-up period. RPV trough concentrations were measured in 384 rectal samples.

Results: 597 plasma and 561 rectal samples from 90 participants were analyzed. HIV-1 RNA >50 (>1.69 log10) copies/swab was detected in 14.7% (59/401) of rectal samples (42.2% of participants) during intramuscular CAB/RPV, and in 17.5% (28/160) of rectal samples (29% of participants) during oral ART. Median (range) detectable rectal HIV-1 RNA level during intramuscular ART was 362 (226-659) copies/swab. The frequency and quantity of rectal shedding did not differ between groups with/without oral lead-in. No correlation was observed between rectal shedding and detectable plasma HIV-1 RNA. Median (Q1-Q3) rectal RPV concentration was 3.07 (2.83-3.35) log10 ng/swab, 1.6-fold above the EC90 for rectal tissue, and did not correlate with rectal HIV-1 RNA levels. Rectal shedding was associated with plasma pre-ART HIV-1 RNA >5 log10 in multivariate Cox regression, but was unrelated to established predictors of virological failure with CAB/RPV.

Conclusion: Rectal HIV-1 shedding is common during bimonthly intramuscular CAB/RPV treatment and is also observed with oral ART. Shedding was independent of concurrent plasma HIV-1 RNA and rectal RPV concentrations, and was associated with pre-ART viral load.

Background: While severe outcomes among hospitalised patients with COVID-19 and influenza are well described, comparative studies on community transmission and milder illnesses associated with COVID-19 and influenza are lacking.

Methods: We compared incidence, risk/protective factors, and clinical features among prospective community cohort participants with PCR-confirmed COVID-19-associated and influenza-associated acute respiratory illnesses (ARI) from 7-February to 2-October 2022 in Wellington, New Zealand.

Findings: The crude COVID-19-associated ARI incidence was 59/100 person-years (PY). The adjusted cumulative incidence for COVID-19 [77/100-PY;95%CI,75-80] was 4.5 times higher than for influenza [17/100-PY;95%CI,15-19]. The proportion of children (0-17 years) with COVID-19 of all COVID-19 cases was substantial but smaller than those of influenza [402/1229 (33%) vs 173/255 (68%), p<0.0001]. The highest incidence of COVID-19 was among adolescents (12-17 years) [109/100-PY;95%CI,97-119] and non-Māori/Pacific [83/100-PY;95%CI,80-86] whereas the highest influenza incidence was among children (1-4 years) [49/100-PY;95%CI,40-58] and Māori [35/100-PY;95%CI,28-43].Adolescents (12-17 years) had 2.5 times higher peak COVID-19 incidence (5.9/100) than adults ≥18 years (2.4/100). Adolescents with two doses of the COVID-19 vaccines had 75% greater risk of COVID-19 infection [hazard ratio:1.75,95%CI,1.40-2.20] compared to adults with three doses.Vaccination, age, ethnicity, and household size were independent protective/risk factors for COVID-19 or influenza.Participants with COVID-19, compared with influenza, were less likely to access healthcare or experience febrile/severe illnesses, but more likely to report sore throat, headache, myalgia, and taste/smell loss.

Interpretation: As the world transitions to COVID-19 endemicity, estimating disease burdens in community settings becomes important to understand complete disease pyramids, risk factors and clinical progression for informing countermeasures.

Purpose: Our goal was to investigate IgG1 and IgG3 antibody responses to Chlamydia trachomatis proteins Pgp3 and Hsp60 in women with tubal factor infertility (TFI). Our goal was to determine the role of these biomarkers in the diagnosis of C. trachomatis-associated TFI, and assess their sensitivity and specificity for detecting tubal pathology.

Methods: Serum samples were collected from 258 subfertile women, and 34 women positive for C. trachomatis by nucleic acid amplification test (NAAT). IgG1 and IgG3 antibodies to Pgp3 and Hsp60 were measured using enzyme immune assays (EIA).

Results: Pgp3 IgG1 antibodies were detected in 68.2% of TFI cases and 31.8% of controls (non-TFI), while Hsp60 IgG1 antibodies were found in 36.4% of TFI cases. Pgp3 IgG1 had the highest sensitivity for TFI (68.2%, 95% CI [45.1-86.1]), while Hsp60 IgG3 was the most specific (93.6%, 95% CI [89.7-96.4]). Antibody levels increased with tubal damage severity. Among the 34 NAAT-positive women, 78.8% were positive for Pgp3 IgG1.

Conclusions: Pgp3 IgG1 antibody was a sensitive marker for detecting C. trachomatis-related TFI, while Hsp60 IgG3 antibody was highly specific. These findings suggest that Pgp3 and Hsp60 antibodies and antibody subclass testing may be useful diagnostic tools for assessing TFI.

Background: Sapovirus is an important cause of acute gastroenteritis in childhood. While vaccines against sapovirus may reduce gastroenteritis burden, a major challenge to their development is a lack of information about natural immunity.

Methods: We measured sapovirus-specific IgG in serum collected between 2017 and 2020 of mothers soon after delivery and at 6 time points in Nicaraguan children until 3 years of age (n = 112 dyads), using virus-like particles representing 3 sapovirus genotypes (GI.1, GI.2, GV.1).

Results: Of the 112 children, 16 (14.3%) experienced at least 1 sapovirus gastroenteritis episode, of which GI.1 was the most common genotype. Seroconversion to GI.1 and GI.2 was most common between 5 and 12 months of age, while seroconversion to GV.1 peaked at 18 to 24 months of age. All children who experienced sapovirus GI.1 gastroenteritis seroconverted and developed genotype-specific IgG. The impact of sapovirus exposure on population immunity was determined by antigenic cartography: newborns share their mothers' broadly binding IgG responses, which declined at 5 months of age and then increased as infants experienced natural sapovirus infections.

Conclusions: By tracking humoral immunity to sapovirus over the first 3 years of life, this study provides important insights for the design and timing of future pediatric sapovirus vaccines.

Background: The clinical impact of plasma metagenomic next-generation sequencing (mNGS) on infection diagnosis and antimicrobial therapy in immunocompromised patients with suspected infection remains unclear.

Methods: Between March and December 2022, 424 cases with fever, infection history, mechanical ventilation, or imaging abnormalities underwent plasma mNGS testing at a single center. Eleven patients had received solid organ transplantation, and the remaining patients were categorized into febrile neutropenia (FN), non-neutropenia (NN), and non-transplant and non-hematologic disease (NTHD) groups based on immunosuppression severity. The diagnostic rate of infection and the utilization of antimicrobial agents based on mNGS were assessed.

Results: The use of mNGS significantly improved the diagnostic rates for fungi in the FN (65.1%, P = .001) and NN (58.8%, P = .008) groups versus the NTHD group (33.3%). Positive impacts associated with therapy were significantly greater than negative impacts across all 3 groups (all P < .001), and the utilization of escalation therapy was significantly more frequent in the FN group than in the NN group (P = .006). More than 70% of cases with negative mNGS results across the 3 groups underwent de-escalation therapy, with more than one-third being discontinued, preventing antimicrobial overuse.

Conclusions: Plasma mNGS has a clinically confirmed positive impact in immunocompromised patients with neutropenia, improving the diagnosis of fungal infections and antimicrobial therapy.