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Abstract Background Nasopharyngeal swabs are taken to determine the causative agent of community acquired pneumonia (CAP), while the reliability of upper respiratory tract sampling as a proxy for lower respiratory tract infections is still unclear. Methods Nasopharyngeal (NP) swabs, bronchoalveolar lavage (BAL) fluid samples and clinical data were collected from 153 hospitalized children between 3 months and 14 years of age with severe CAP, enrolled from March to June 2019. Written informed consent for the storage and use of the samples for further studies was obtained from the parents or caregivers. Putative pathogens were detected using a sensitive, high-throughput GeXP-based multiplex PCR and qPCR. Results The same bacterial species in paired samples were found in 29 (23.4%) and the same viral species in 52 (27.5%) of the patients. moderate concordance was found for Mycoplasma pneumoniae (ĸ=0.64), followed by Haemophilus influenzae (ĸ=0.42). The strongest discordance was observed for human adenovirus and also for Pseudomonas aeruginosa, the latter was exclusively detected in BAL samples. In the adenovirus cases strong concordance was associated with high viral loads in the NP swabs. Conclusion The variation in concordance in pathogen detection in the upper and lower respiratory tract of children with severe pneumonia is generally high but varies depending on the species. Novel and impactful insights are the concordance between NP and BAL detection for M. pneumoniae and H. influenzae and the strong correlation between high adenoviral loads in NP swabs and detection in BAL fluid. …

Abstract Background Understanding Plasmodium falciparum population diversity and transmission dynamics provides information on the intensity of malaria transmission, which is needed for assessing malaria control interventions. This study aimed to determine P. falciparum allelic diversity and multiplicity of infection (MOI) among asymptomatic and symptomatic school-age children in Kinshasa Province, Democratic Republic of Congo (DRC). Methods A total of 438 DNA samples (248 asymptomatic and 190 symptomatic) were characterized by nested PCR and genotyping the polymorphic regions of pfmsp1 block 2 and pfmsp2 block 3. Results Nine allele types were observed in pfmsp1 block2. The K1-type allele was predominant with 78% (229/293) prevalence, followed by the MAD20-type allele (52%, 152/293) and RO33-type allele (44%, 129/293). Twelve alleles were detected in pfmsp2, and the 3D7-type allele was the most frequent with 84% (256/304) prevalence, followed by the FC27-type allele (66%, 201/304). Polyclonal infections were detected in 63% (95% CI 56, 69) of the samples, and the MOI (SD) was 1.99 (0.97) in P. falciparum single-species infections. MOIs significantly increased in P. falciparum isolates from symptomatic parasite carriers compared with asymptomatic carriers (2.24 versus 1.69, adjusted b: 0.36, (95% CI 0.01, 0.72), p = 0.046) and parasitaemia > 10,000 parasites/µL compared to parasitaemia < 5000 parasites/µL (2.68 versus 1.63, adjusted b: 0.89, (95% CI 0.46, 1.25), p < 0.001). Conclusion This survey showed low allelic diversity and MOI of P. falciparum, which reflects a moderate intensity of malaria transmission in the study areas. MOIs were more likely to be common in symptomatic infections and increased with the parasitaemia level. Further studies in different transmission zones are needed to understand the epidemiology and parasite complexity in the DRC. …

Infection and Immunity, Ahead of Print.

Infection and Immunity, Ahead of Print.

The emergence of SARS-CoV-2 causing the prolonged COVID-19 pandemic has had profound public health and socio-economic consequences worldwide [1]. Throughout the course of the pandemic, the rapid mutation of SARS-CoV-2 has spawned numerous novel strains including variants of concern (VOCs) – further complicating infection control measures with altered transmissibility, virulence, and immune evasion [2,3]. Currently, the world is gradually transitioning to endemicity with the rapid spread and dominance of the Omicron VOC and its subvariants.

Peritonitis is a common complication of peritoneal dialysis (PD), which is significantly related to the mortality of PD patients [1]. Mycoplasma hominis, Ureaplasma parvum, and Ureaplasma urealyticum commonly colonize the urogenital tract [2]. PD-associated peritonitis caused by them has rarely been reported. Herein, we reported four cases of this disease and reviewed the literature.

Objectives We assessed the effect of inactivated COVID-19 vaccine boosting immunization on the viral shedding time for patients infected with the Omicron variant BA.2.Methods We performed a real-world study by analyzing outbreak data of patients infected with the COVID-19 Omicron variant BA.2 from March to May 2022 in Shanghai, China. Patients were categorized into three groups, including not fully vaccinated (0 and 1 dose), fully vaccinated (2 doses), and booster-vaccinated (3 doses).Results A total of 4443 patients infected with COVID-19 were included in the analysis.

Puumala virus (PUUV) is a hantavirus causing haemorrhagic fever with renal syndrome. Studies showing an increased risk of lymphoid malignancies following hantavirus infection, together with the observation that PUUV infects B cells motivated us to study the risk of lymphoid malignancies following PUUV infection.

This winter is particularly noteworthy, as common viruses are making a resurgence and spreading at an alarming rate, with an unprecedented outbreak of Respiratory Syncytial Virus (RSV) currently ongoing. It is important to remember that RSV can also pose a significant threat to the elderly and those with underlying health conditions [1], which is often overlooked given the focus on bronchiolitis in healthy children and the associated risk of hospitalization [2]. This is particularly concerning, as RSV is believed to be responsible for 14,000 deaths per year in the USA for people aged 65 and over; and it is estimated to cause the deaths of approximately 100,000 children worldwide annually.

The World Health Organization (WHO) estimated that about 10.6 million people fell ill with tuberculosis (TB) worldwide in 2021, equivalent to 134 cases per 100,000 inhabitants [1-3]. Children aged under 15 years account for about 11% of TB cases, meaning >1 million new pediatric cases in 2021 [1, 3]. There were an estimated 1.6 million deaths due to TB in 2021, of which 14% involved children [1, 3]. Up to 80% of deaths occurred in children aged under 5 years [4].

Coronavirus Disease-19 (COVID 19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) are the two leading causes of death in the world [1–3].

fHbp is a virulence factor expressed by the human-specific pathogen N. meningitidis, a leading cause of meningitis and sepsis worldwide which frequently asymptomatically colonizes the human upper airway. fHbp binds human CFH, a negative regulator of the complement system, and has multiple roles during meningococcal infection. fHbp was initially identified as a vaccine antigen, named GNA1870 [1] or LP2086 [2]. It was then shown that the meningococcus binds CFH to its surface via an ~33 kDa protein, promoting bacterial survival in serum [3].

There is a scarcity of data on outcomes and predictors of therapeutic failure of mAbs in frail COVID-19 patients.

AbstractBackgroundALPK1 agonist has recently been reported to demonstrate anti-HBV efficacy via activating NF-κB signaling, which is crucial for maximizing interferon responses. Here, we investigated the impact of ALPK1 on HBV replication, and explored ALPK1 variants for predicting PegIFNα treatment response.MethodsThe potential anti-HBV effect of ALPK1 was evaluated in HBV-integrated and HBV-infected hepatoma cells. The potentially functional genetic variants of ALPK1 were screened out and their correlations with PegIFNα treatment response were assessed in 945 HBeAg-positive chronic hepatitis B (CHB) patients.ResultsWe revealed that ALPK1 inhibited HBV replication in hepatocytes via activating the JAK-STAT pathway. ALPK1 overexpression improved the anti-HBV effect of IFNα in cell models. A missense variant, rs35389530 (P660L), of ALPK1 was strongly associated with combined response (CR, namely HBeAg seroconversion and HBV DNA level <3.3log10IU/ml) to PegIFNα treatment in CHB patients (P = 2.12 × 10−6). Moreover, a polygenic score (PGS) integrating ALPK1_rs35389530 and two additional genetic variants was further significantly associated with CR (Ptrend = 9.28 × 10−7), HBsAg level (Ptrend = 0.0002), and HBsAg loss (Ptrend = 0.025).ConclusionsThe anti-HBV effects of ALPK1 through activating JAK-STAT pathway provides a new perspective for CHB therapy. ALPK1_rs35389530 and PGS are potential biomarkers to predict PegIFNα treatment response and may be utilized for optimizing CHB treatment.

AbstractInfection with intestinal whipworms (Trichuris spp.) causes widespread morbidity and may alter responses to enteric and extraintestinal co-infections. Here, we show that Trichuris muris infection in mice increases co-infection with two evolutionary divergent enteric pathogens, the bacterium Citrobacter rodentium and the helminth Heligmosomoides polygyrus. Co-infection caused reduced weight gain and promoted type-1-biased inflammation. In contrast, T. muris-infected mice were more resistant to migrating Ascaris suum larvae in the lungs. Our results highlight the divergent nature of pathogen interactions, and suggest that whipworm infection is a risk-factor for co-infections with other pathogens within the gastrointestinal tract.

AbstractInpatient direct oral challenge programs are increasingly deployed as part of antimicrobial stewardship (AMS) initiatives to reduce the burden and impacts of penicillin allergy labels on antibiotic prescribing. Using data from a prospective multicentre cohort inpatient penicillin allergy program, we identify the key targets for delabeling to aid health service implementation.

AbstractBackgroundLaboratory tests to diagnose neurosyphilis using cerebrospinal fluid (CSF) are currently disadvantageous as a lumbar puncture is required, which may result in patients with neurosyphilis missing an opportunity for early diagnosis. Thus, blood biomarker candidates that are more convenient and minimally invasive to collect for diagnosing neurosyphilis is urgently needed.MethodsThis observational study aimed to analyze serum ubiquitin C-terminal hydrolase-L1 (UCH-L1), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NF-L) levels in 153 patients without HIV and to evaluate their diagnostic performance in neurosyphilis compared with CSF.ResultsSerum UCH-L1, GFAP, and NF-L levels were significantly higher in patients with neurosyphilis compared with patients with uncomplicated syphilis or non-syphilis. For the diagnosis of neurosyphilis, serum UCH-L1, GFAP, and NF-L revealed sensitivities of 90.20%, 80.40%, and 88.24%, and specificities of 92.16%, 78.43%, and 80.39%, respectively, at cut-off levels of 814.50 pg/mL, 442.70 pg/mL, and 45.19 pg/mL, respectively. In patients with syphilis, serum UCH-L1, GFAP, and NF-L levels correlated strongly or moderately with those in the CSF, with similar or better diagnostic performance than those in the CSF. The testing algorithms’ sensitivity and specificity increased to 98.04% and 96.08%, respectively, when subjected to parallel and combination testing, respectively.ConclusionTo avoid lumbar puncture, each serum UCH-L1, GFAP, and NF-L is a good entry point and biomarker candidate for the diagnosis of neurosyphilis among patients without HIV. These proteins used in concerto can further improve the diagnostic sensitivity and specificity.

AbstractThe human gut harbors native microbial communities, forming a highly complex ecosystem. Synthetic microbial communities (SynComs) of the human gut are an assembly of microorganisms isolated from human mucosa or fecal samples. In recent decades, the ever-expanding culturing capacity and affordable sequencing, together with advanced computational modeling, started a ‘‘golden age’’ for harnessing the beneficial potential of SynComs to fight gastrointestinal disorders, such as infections and chronic inflammatory bowel diseases. As simplified and completely defined microbiota, SynComs offer a promising reductionist approach to understanding the multi-species and multi-kingdom interactions in the microbe-host-immune axis. However, there are still many challenges to overcome before we can precisely construct SynComs of designed function and efficacy that allow the translation of scientific findings to patients' treatments. Here we discussed the strategies used to design, assemble, and test a SynCom, and address the significant challenges, which are of microbiological, engineering, and translational nature, that stand in the way of using SynComs as live bacterial therapeutics.

Chora and colleagues show that infection of the liver by Plasmodium modulates severity of disease in the experimental cerebral malaria (ECM) model by generating gamma delta (ɣδ) T cells that produce IL-17. This work calls into question the long-standing assumption that liver infection does not modulate severity of malaria.

Parasite worms or helminths (see Glossary) are parasites of almost all vertebrates, including humans as well as wild and domestic mammals. Globally, helminths affect nearly a quarter of the human population, essentially infecting individuals living under poor hygienic conditions in low- and middle-income countries [1]. Such an epidemiologic situation explains the large geographic overlap between regions where helminth infections are endemic and areas where diseases caused by heterologous agents such as tuberculosis, malaria, or infection by HIV are prevalent.

Microbial communities that degrade natural polysaccharides are thought to have a hierarchical organization and one-way positive interactions from higher to lower trophic levels. Daniels et al. have recently shown that reciprocal interactions between trophic levels can occur and that these interactions change over the duration of a batch culture.

Abstract Purpose Overweight and obesity have increased in people living with HIV (PLH). Our study evaluated weight, body-mass-index (BMI), and waist-to-hip ratio (WHR) change over 5 years of follow-up in PLH compared to the general population. Methods HIV-positive participants in the HIV Heart Aging (HIVH) study were matched 1:2 by age and sex with HIV-negative controls of the population-based Heinz Nixdorf Recall (HNR) study. Both studies were recruited in the German Ruhr area. The association between HIV and weight, BMI, and WHR changes was examined using linear regression. Regression models were adjusted for parameters potentially affecting weight gain. Results The matched HIVH and HNR participants (N = 585 and N = 1170, respectively; 14.7% females) had a mean age of 55 years at baseline. Despite the lower baseline weight (− 6 kg, 95% CI − 7.46 to − 4.59), the linear regression showed greater absolute and relative weight and BMI increases after 5 years in HIVH compared to HNR. Adjusting the linear regression models for smoking amplified that HIVH had a higher absolute and relative weight difference of 0.7 kg or ~ 1% compared to HNR after 5 years (95% Cl 0.1 to 1.3 and 0.2 to 1.6, respectively). Adjusting for HDL, LDL, systolic blood pressure, and diabetes mellitus did not affect the results. Conclusions PLH had lower weight than the general population at baseline and after 5 years, but experienced greater increases in body weight after 5 years. WHR change after 5 years was lower in PLH compared to the general population, despite a higher WHR at baseline. …

Abstract Purpose Lung transplant (LTx) recipients are at risk for poor outcomes from coronavirus disease 2019 (COVID-19). The aim of the study was to assess the outcome of patients receiving pre-exposure prophylaxis (PrEP) with tixagevimab and cilgavimab after LTx. Methods All LTx recipients with outpatient visits from February 28th to October 31st, 2022 at two German centers were included. Baseline characteristics were recorded and patients followed until November 30rd, 2022. Infections with SARS-CoV-2, disease severity, and COVID-19-associated death were compared between patients with and without PrEP. Results In total, 1438 patients were included in the analysis, and 419 (29%) received PrEP. Patients receiving PrEP were older and earlier after transplantation, had lower glomerular filtration rates, and lower levels of SARS-CoV-2-S antibodies. In total, 535 patients (37%) developed SARS-CoV-2 infection during a follow-up of median of 209 days. Fewer infections occurred in patients with PrEP during the study period (31% vs. 40%, p = 0.004). Breakthrough SARS-CoV-2 infections after PrEP occurred in 77 patients (19%). In total, 37 infections (8%) were severe or critical. No difference in severity of COVID-19 was observed between patients with and without PrEP. There were 15 COVID-19-associated deaths (n = 1 after PrEP). Compared to matched controls, there was a non-significant difference towards a lower risk for moderate to critical COVID-19 (p 0.184). Conclusion The number of SARS-CoV-2 infections was lower in LTx recipients with PrEP. Despite being at higher risk for worse outcome severity of COVID-19 and associated mortality were similar in patients with and without PrEP. …