Severe acute herpes virus type 2 primo-infection and its association with anti-type 1 interferon autoantibodies.

Herpes simplex virus type 2 (HSV-2) is a common cause of infection, which is usually self-limited and asymptomatic. A 71-year-old patient with HSV-2 primo-infection developed acute hepatitis and secondary hemophagocytic lymphohistiocytosis. The patient had high levels of autoantibodies against type I interferon (IFN) (> 1000 ng/mL), neutralizing high concentration (10 ng/mL) of both IFN-α and IFN-ω but not IFN-ß. Anti-IFN-I auto-antibodies are rarely observed in healthy individuals; however, their prevalence increases in individuals over 70 years of age and have been identified as a cause of some severe viral diseases, including critical COVID-19. Considering the function of IFN-I in innate immunity, the pathological role of these autoantibodies in severe viral diseases following primo-infections in elderly patient appears crucial.

Progressive Multifocal Leukoencephalopathy after Treatment with Nivolumab.

Progressive multifocal leukoencephalopathy (PML) is increasingly being reported in patients undergoing immunotherapy. We report a case of progressive multifocal leukoencephalopathy after treatment with nivolumab, a PD-1 blocker that is used to restore impaired T-cell responses in patients with cancer and infections. Data for 4 other cases were obtained from pharmacovigilance databases.

Dolutegravir reshapes the genetic diversity of HIV-1 reservoirs.

Objectives: Better understanding of the dynamics of HIV reservoirs under ART is a critical step to achieve a functional HIV cure. Our objective was to assess the genetic diversity of archived HIV-1 DNA over 48 weeks in blood cells of individuals starting treatment with a dolutegravir-based regimen. Methods: Eighty blood samples were prospectively and longitudinally collected from 20 individuals (NCT02557997) including: acutely (n = 5) and chronically (n = 5) infected treatment-naive individuals, as well as treatment-experienced individuals who switched to a dolutegravir-based regimen and were either virologically suppressed (n = 5) or had experienced treatment failure (n = 5). The integrase and V3 loop regions of HIV-1 DNA isolated from PBMCs were analysed by pyrosequencing at baseline and weeks 4, 24 and 48. HIV-1 genetic diversity was calculated using Shannon entropy. Results: All individuals achieved or maintained viral suppression throughout the study. A low and stable genetic diversity of archived HIV quasispecies was observed in individuals starting treatment during acute infection. A dramatic reduction of the genetic diversity was observed at week 4 of treatment in the other individuals. In these patients and despite virological suppression, a recovery of the genetic diversity of the reservoirs was observed up to 48 weeks. Viral variants bearing dolutegravir resistance-associated substitutions at integrase position 50, 124, 230 or 263 were detected in five individuals (n = 5/20, 25%) from all groups except those who were ART-failing at baseline. None of these substitutions led to virological failure. Conclusions: These data demonstrate that the genetic diversity of the HIV-1 reservoir is reshaped following the initiation of a dolutegravir-based regimen and strongly suggest that HIV-1 can continue to replicate despite successful treatment.

Dual detection of Neoehrlichia mikurensis and Anaplasma phagocytophilum: How biplex PCR led in France to the diagnosis of neoehrlichiosis in post-tick bite fever.

OBJECTIVES: Neoehrlichia mikurensis (NM) is an emerging intracellular bacterium member of the Anaplasmatacecae family. So far, only four cases have been described in France, all of them retrospectively. METHODS: This study describes two new cases of NM discovered following implementation of a biplex PCR targeting both Anaplasma and NM. RESULTS: Two immunocompetent patients developed a flu-like illness within 14 days after an identified tick bite. Both had negative Anaplasma PCR, but by using this biplex PCR NM, infection was diagnosed in both cases. One patient recovered spontaneously while the second was successfully treated by a seven-day course of doxycycline. CONCLUSION: Present in Eastern France, NM is underdiagnosed. Biplex PCR screening of NM with A.phagocytophilum could effectively address this issue.

Nosocomial Coronavirus Disease 2019 during 2020-2021: Role of Architecture and Ventilation.

Nosocomial coronavirus disease 2019 (COVID-19) is a major airborne health threat for inpatients. Architecture and ventilation are key elements to prevent nosocomial COVID-19 (NC), but real-life data are challenging to collect. We aimed to retrospectively assess the impact of the type of ventilation and the ratio of single/double rooms on the risk of NC (acquisition of COVID-19 at least 48 h after admission). This study was conducted in a tertiary hospital composed of two main structures (one historical and one modern), which were the sites of acquisition of NC: historical (H) (natural ventilation, 53% single rooms) or modern (M) hospital (double-flow mechanical ventilation, 91% single rooms). During the study period (1 October 2020 to 31 May 2021), 1020 patients presented with COVID-19, with 150 (14.7%) of them being NC (median delay of acquisition, 12 days). As compared with non-nosocomial cases, the patients with NC were older (79 years vs. 72 years; p < 0.001) and exhibited higher mortality risk (32.7% vs. 14.1%; p < 0.001). Among the 150 NC cases, 99.3% were diagnosed in H, mainly in four medical departments. A total of 73 cases were diagnosed in single rooms versus 77 in double rooms, including 26 secondary cases. Measured air changes per hour were lower in H than in M. We hypothesized that in H, SARS-CoV-2 transmission was favored by short-range transmission within a high ratio of double rooms, but also during clusters, via far-afield transmission through virus-laden aerosols favored by low air changes per hour. A better knowledge of the mechanism of airborne risk in healthcare establishments should lead to the implementation of corrective measures when necessary. People's health is improved using not only personal but also collective protective equipment, i.e., ventilation and architecture, thereby reinforcing the need to change institutional and professional practices.

Impact of Different Anthropogenic Environments on Ticks and Tick-Associated Pathogens in Alsace, a French Region Highly Endemic for Tick-Borne Diseases.

Ticks and tick-borne diseases have spread over the last decades. In parallel, the incidence in humans, accidental hosts for most of these zoonotic diseases, has increased. This epidemiological intensification can be associated with anthropogenic alterations of forest ecosystems and animal biodiversity, but also with socioeconomic changes. Their proliferation is largely due to human-induced effects on the factors that favor the circulation of these infectious agents. We selected different types of anthropogenic environments in Alsace, a region endemic for tick-borne diseases in France, to better understand the impact of human interventions on tick populations and tick-borne disease incidence. Ticks were collected in one golf course, three urban parks, one mid-mountain forest, and one alluvial forest that is currently part of a protected natural area. Ixodes ricinus was found primarily in humid vegetation, which is favorable for tick survival, such as grounds populated with trees and covered with leaf litter. We also observed that reforestation and high animal biodiversity in a protected area such as the alluvial forest led to a greater number of ticks, including both Ixodes ricinus and Dermacentor reticulatus, as well as to a higher prevalence of pathogens such as Borrelia burgdorferi sensu lato, Anaplasma phagocytophilum, Borrelia miyamotoi, and Rickettsia raoulti.

Case Report: A New Gain-of-Function Mutation of STAT1 Identified in a Patient With Chronic Mucocutaneous Candidiasis and Rosacea-Like Demodicosis: An Emerging Association.

Purpose: Heterozygous missense STAT1 mutations leading to a gain of function (GOF) are the most frequent genetic cause of chronic mucocutaneous candidiasis (CMC). We describe the case of a patient presenting a new GOF mutation of STAT1 with the clinical symptoms of CMC, recurrent pneumonia, and persistent central erythema with papulopustules with ocular involvement related to rosacea-like demodicosis. Methods: Genetic analysis via targeted next-generation sequencing (NGS; NGS panel DIPAI v.1) exploring the 98 genes most frequently involved in primary immunodeficiencies, including STAT1, was performed to identify an underlying genetic defect. Results: NGS identified a novel variant of STAT1, c.884C>A (exon 10), p.T295Y, not previously described. This variant was found to be gain of function using an in vitro luciferase reporter assay. Rosacea-like demodicosis was confirmed by substantial Demodex proliferation observed via the microscopic examination of a cutaneous sample. A review of literature retrieved 20 other cases of STAT1 GOF mutations associated with early-onset rosacea-like demodicosis, most with ocular involvement. Conclusion: We describe a new STAT1 GOF mutation associated with a phenotype of CMC and rosacea-like demodicosis. Rosacea-like demodicosis appears as a novel and important clinical phenotype among patients with STAT1 GOF mutation.

Acute renal failure related to high doses of acyclovir (15 mg/kg/8 h) during treatment of varicella zoster virus encephalitis.

Varicella zoster virus (VZV) is less susceptible than herpes simplex virus to acyclovir. The optimal acyclovir regimen during VZV encephalitis remains unknown. We report two cases of acute renal failure after an increase in acyclovir dosage from 10 mg to 15 mg/kg/8 h during the treatment of VZV encephalitis according to French guidelines.