Journal of Infectious Diseases

BACKGROUND: Targeting multiple key antigens that mediate distinct P. falciparum erythrocyte invasion pathways is an attractive approach for the development of blood-stage malaria vaccines. However, the challenge is to identify antigen cocktails that elicit potent strain-transcending parasite-neutralizing antibodies efficacious at low IgG concentrations feasible to achieve through vaccination. Previous reports have screened inhibitory antibodies primarily against well-adapted laboratory parasite clones...

BACKGROUND: Human polyomaviruses (HPyVs) have been associated with several cutaneous inflammatory conditions. More investigation is needed to identify further presentations of cutaneous pathology associated with HPyVs. Our aim was to investigate the possible association of skin-tropic HPyVs with folliculitis, particularly eosinophilic pustular folliculitis (EPF). METHODS: This study included 55 Japanese patients, comprising 13 patients with EPF and 42 patients with suppurative folliculitis...

BACKGROUND: Several preclinical and clinical investigations have argued for nervous system involvement in SARS-CoV-2 infection. Some sparse case reports have described various forms of encephalitis in COVID-19 disease, but very few data have focused on clinical presentations, clinical course, response to treatment and outcomes. METHODS: The ENCOVID multicentre study included patients with encephalitis with full infectious screening, CSF, EEG, MRI data and confirmed SARS-CoV-2 infection recruited from 13 centres in northern Italy...

BACKGROUND: Human herpesvirus 6 (HHV-6) can be genetically transmitted from parent to child as inherited chromosomally integrated HHV-6 (iciHHV-6). HHV-6 reactivation occurs in pregnant women with iciHHV-6. We showed no gender differences in the frequency of index cases with iciHHV-6 but inheritance from the father was more common. We evaluated the association between iciHHV-6 status and spontaneous abortion. METHODS: iciHHV-6 was confirmed by high viral DNA copy numbers in whole blood and somatic cells...

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BACKGROUND: Dengue is a global health problem, and the development of a tetravalent dengue vaccine with durable protection is a high priority. A heterologous prime boost strategy has the advantage of eliciting immune responses through different mechanisms and therefore may be superior to homologous prime boost strategies for generating durable tetravalent immunity. METHODS: In this phase 1 first in human heterologous prime boost study, 80 volunteers were assigned to 4 groups and received a tetravalent dengue virus (DENV-1-4) purified inactivated vaccine (TDENV-PIV) with alum adjuvant and a tetravalent dengue virus (DENV-1-4) live attenuated vaccine (TDENV-LAV) in different orders and dosing schedules (28 or 180 days apart)...

BACKGROUND: Respiratory syncytial virus (RSV) generally causes mild disease but can cause severe infections in (premature) infants and elderly adults. Here, we studied RSV-specific antibody concentrations throughout life with emphasis on infants and chronic obstructive pulmonary disease (COPD) patients. METHODS: Sera (N = 2655) from 2 nationwide cross-sectional studies in the Netherlands including individuals aged 0-90 years were analyzed for IgG and IgA antibodies to RSV prefusion F, postfusion F, N, Ga, and Gb proteins and for antibody avidity in 42 COPD patients...

BACKGROUND: Whether accelerated aging develops over the course of chronic HIV infection or can be observed prior to significant immunosuppression on is unknown. We studied DNA methylation in blood to estimate cellular aging in persons living with HIV (PLWH) prior to the initiation of antiretroviral therapy. METHODS: 378 antiretroviral therapy-naïve PLWH with CD4 T cell counts >500 cells/mm 3 enrolled in the Strategic Timing of Antiretroviral Therapy trial (Pulmonary Substudy) were compared to 34 HIV-negative controls...

BACKGROUND: Babesia microti, a malaria-like pathogen, is increasing in mammal and human populations in endemic areas and is unlikely to be the sole result of horizontal pathogen transmission. METHODS: Peromyscus leucopus mice, natural reservoir hosts, were infected via Ixodes scapularis nymphs. Infected parental females (n = 6) produced F1 offspring (n = 36) that were screened for B. microti using quantitative PCR. Xenodiagnostic larvae were fed on infected offspring to determine horizontal transmission and pathogen viability...

BACKGROUND: Mycobacterium tuberculosis (Mtb), the bacterium that causes tuberculosis (TB), causes 10 million infections and 1.5 million deaths per year worldwide. The success of Mtb as a human pathogen is directly related to its ability to suppress host responses, which are critical for clearing intracellular pathogens. Emerging evidence suggests that key response pathways may be regulated by a novel class of small non-coding RNA, called tRNA-derived fragments (tRFs). tRFs can complex with Argonaute proteins to target and degrade mRNA targets, similarly to miRNAs, but have thus far been overlooked in the context of bacterial infections...

BACKGROUND: Secondary bacterial coinfections are ranked as a leading cause of hospitalization and morbidity associated with influenza. Because vitamin A deficiencies (VAD) and insufficiencies are frequent in both developed and developing countries, we asked how VAD influences coinfection severity. METHODS: VAD and control mice were infected with influenza virus for evaluation of inflammatory cytokines, cellular immune responses, and viral clearance. Influenza-infected mice were coinfected with Streptococcus pneumoniae to study weight loss and survival...

Atypical mononuclear cells (AM) appear in significant numbers in peripheral blood of patients with Epstein-Barr virus (EBV)-associated infectious mononucleosis (IM). We have investigated the number and lineage-specific clusters of differentiation (CD) expression of the atypical mononuclear cells in 110 children with IM using the anti-CD antibody microarray for panning the leukocytes by their surface markers prior to morphology examination. We show that AM population consists primarily of CD8+ T-cells with a small fraction (0-2% of all lymphocytes) of CD19+ B-lymphocytes...

To date, no vaccine or monoclonal antibody (mAb) against S. aureus has been approved for use in humans. Our lab has developed a five-antigen S. aureus vaccine (rFSAV), which is now under efficacy evaluation in a phase II clinical trial. In the current study, using overlapping peptides and antiserum from rFSAV-immunized volunteers, we identified seven B-cell immunodominant epitopes on 4 antigens in rFSAV, including five novel epitopes (Hla48-65, IsdB402-419, IsdB432-449, SEB78-95 and MntC7-24). Ten immunodominant-epitope mAbs were generated against these epitopes, and all of them exhibited partial protection in a mouse sepsis model...

BACKGROUND: Although Mycoplasma pneumoniae (MP) infection has been implicated in the pathogenesis of allergic diseases, the mechanism of this trigger remains unknown. OBJECTIVE: We explored the mechanism for how MP infection could tilt the balance between regulatory T cells (Tregs) and Th17 cells. METHODS: We analyzed the frequency, phenotype, and function of Tregs in patients at the different stages of MP and various virus infections over a period of more than 1 year...

Recurrent lymphocytic meningitis (RLM), also referred to as Mollaret's meningitis is a rare neuro-disease characterized mainly by reactivation of herpes simplex virus (HSV)-2 from sensory ganglia. However, the underlying host immune determinants and viral factors rendering some individuals unable to maintain HSV-2 latency are largely unknown. We collected a cohort of fifteen patients diagnosed with Mollaret's meningitis. By whole exome sequencing we identified rare host genetic variants predicted to be deleterious in molecules involved in i) ubiquitin-proteasome pathways, ii) the autophagy machinery, and iii) cell proliferation/apoptosis...

The COVID-19 pandemic in the United States has revealed major disparities in the access to testing and messaging about the pandemic based on the geographic location of individuals, particularly in communities of color, rural areas, and areas of low income. This geographic disparity, in addition to deeply rooted structural inequities, have posed additional challenges to adequately diagnose and provide care for individuals of all ages living in these settings. We describe the impact that COVID-19 has had on geographic disparate populations in the United States and share our recommendations to what might be done to ameliorate the current situation...

The 2020 SARS-CoV-2 pandemic is caused by a zoonotic coronavirus transmitted to humans, similar to earlier events. Whether the other, seasonally circulating coronaviruses induce cross-reactive, potentially even cross-neutralizing antibodies to the new species in humans is unclear. The question is of particular relevance for people with immune deficiencies, as their health depends on treatment with immunoglobulin preparations that need to contain neutralizing antibodies against the pathogens in their environment...

BACKGROUND: An unbiased approach of SARS-CoV-2-induced immune dysregulation has not been undertaken so far. We aimed to identify previously unreported immune markers able to discriminate COVID-19 patients from healthy controls and to predict mild and severe disease. METHODS: An observational, prospective, multicentric study was conducted in patients with confirmed COVID-19: mild/moderate (n=7) and severe (n=19). Immunophenotyping of whole blood leukocytes was performed in patients upon hospital ward or intensive care unit admission and in healthy controls (n=25)...

Plasmodium vivax has two invasion ligand/host receptor pathways (PvDBP/DARC and PvRBP2b/TfR1) that are promising targets for therapeutic intervention. We optimized invasion assays with isogenic cultured reticulocytes. Using a receptor blockade approach with multiple P. vivax isolates, we found that all strains utilized both DARC and TfR1, however with significant variation in receptor usage. This suggests that P. vivax, like P. falciparum, uses alternative invasion pathways with implications for pathogenesis and vaccine development...

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