Revisiting Cytomegalovirus Serology in Allogeneic Hematopoietic Cell Transplant Recipients.

BACKGROUND: Allogeneic hematopoietic cell transplant recipients (allo-HCTRs) with positive cytomegalovirus (CMV) serology may have false-positive results due to blood product transfusion-associated passive immunity. METHODS: This single-center cohort study included allo-HCTRs with negative baseline (at malignancy diagnosis) CMV serology and indeterminate/low-positive (CMV IgG titer, ≥0.6-<50 U/mL) pretransplant CMV serology with negative pretransplant plasma CMV DNAemia. The CMV status of those patients was reclassified from R+ to R- (CMVR- reclassification group). We compared those patients to allo-HCTRs with negative (CMV IgG titer <0.6 U/mL) pretransplant CMV IgG (CMVR- group). We describe the number and type of patients whose pretransplant CMV status was reclassified from indeterminate/positive to negative. We reviewed all plasma CMV DNAemia tests performed during the first 6 months posttransplant in both groups to assess the safety of this approach. RESULTS: Among 246 (84.5%) of 291 transplanted patients identified as CMVR+ pretransplant, 60 (24.4%) were reclassified from CMV serology indeterminate (N:10)/low-positive (N:50) to R-. Only 1 of 60 patients (1.67%) in the CMVR- reclassification group versus 3 of 44 (6.8%; P = .30) in the CMVR- group developed CMV DNAemia during the follow-up period. There were no significant differences in the number of CMV DNAemia tests performed, CMV DNAemia range, and time posttransplant between the 2 groups. CONCLUSIONS: One of 4 allo-HCT CMVR+ may be falsely flagged as R+, with significant impact on donor selection and prophylaxis administration. A 2-step approach including CMV serology testing at hematologic malignancy diagnosis in allo-HCT candidates and careful review of pretransplant CMV IgG titers may help correctly classify CMV serology status.

Identification of a measles variant displaying mutations impacting molecular diagnostics, Geneva, Switzerland, 2023.

Real-time PCR is one of the most widely used techniques to diagnose measles cases. Here we report measles virus variants with three genetic mutations in the reverse primer annealing site of a widely used PCR. The mutations result in a slight loss of the PCR sensitivity. Variants bearing the three mutations presently circulate in different countries since at least the end of 2021. Our findings highlight the usefulness of molecular surveillance in monitoring if oligonucleotides in diagnostic tests remain adequate.

A Case of Mpox Reinfection.

A healthy young man first diagnosed with mpox in May 2022 presented again in November 2022 with anal proctitis and a positive polymerase chain reaction on a rectal swab for Monkeypox virus after a recent trip to Brazil, where he engaged in condomless sexual intercourse with multiple male partners.

[Varicella-zoster virus (VZV) acute retinal necrosis and recombinant zoster vaccine]. / Nécrose rétinienne aiguë due au virus de la varicelle et du zona et vaccin recombinant contre le zona.

Varicella zoster virus (VZV) is responsible for chickenpox. Like all herpes viruses, after primary infection it enters into latency and can be reactivated afterwards. Many forms of symptomatic reactivation of VZV exist including acute retinal necrosis (ARN), an ophthalmic emergency which can lead to blindness. ARN is treated starting with high-dose intravenous acyclovir then with oral valaciclovir for a total duration of up to 3 months. Symptomatic reactivations of VZV are public health issues. The new Swiss 2022 vaccination plan includes the recombinant vaccine Shingrix. It effectively prevents VZV symptomatic reactivations even in elderly and immuno suppressed patients.

Le virus de la varicelle et du zona (VZV) est responsable de la varicelle. Comme tous les virus herpétiques, après la primo-infection, il entre en latence et peut se réactiver plus tard. Il existe de nombreuses formes de réactivations symptomatiques du VZV, dont la nécrose rétinienne aiguë (NRA), qui est une urgence ophtalmique pouvant aboutir à la cécité. La NRA est traitée par aciclovir intraveineux à haute dose dans sa prise en charge initiale puis par valaciclovir per os pour une durée totale pouvant aller jusqu'à 3 mois. Les réactivations symptomatiques de VZV sont un enjeu de santé publique. Le nouveau plan de vaccination suisse 2022 intègre le vaccin recombinant Shingrix, qui permet de prévenir efficacement les réactivations symptomatiques de VZV chez les patients même âgés et immunosupprimés.

Cerebrospinal Fluid Features in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Reverse Transcription Polymerase Chain Reaction (RT-PCR) Positive Patients.

This study analyzed the cerebrospinal fluid features of 31 coronavirus disease 2019 (COVID-19) patients with neurological complications. We observed neither severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in the cerebrospinal fluid, nor intrathecal immunoglobulin G (IgG) synthesis but did observe signs of blood-brain barrier disruption. These results might serve as a basis for a better understanding of SARS-CoV-2 related neuropathogenesis.

Puumala Virus Infection in Family, Switzerland.

We report 3 cases of Puumala virus infection in a family in Switzerland in January 2019. Clinical manifestations of the infection ranged from mild influenza-like illness to fatal disease. This cluster illustrates the wide range of clinical manifestations of Old World hantavirus infections and the challenge of diagnosing travel-related hemorrhagic fevers.

Diagnostic Accuracy of SARS-CoV-2 Rapid Antigen Detection Testing in Symptomatic and Asymptomatic Children in the Clinical Setting.

Antigen-based rapid diagnostic tests (RDTs) are used in children despite the lack of data. We evaluated the diagnostic performance of the Panbio-COVID-19 Ag Rapid Test Device (P-RDT) in children. Symptomatic and asymptomatic participants 0 to 16 years old had two nasopharyngeal swabs (NPS) for both reverse transcription-PCR (RT-PCR) and P-RDT. A total of 822 participants completed the study, of which 533 (64.9%) were symptomatic. Among the 119 (14.5%) RT-PCR-positive patients, the P-RDT sensitivity was 0.66 (95% confidence interval [CI] 0.57 to 0.74). Mean viral load (VL) was higher among P-RDT-positive patients than negative ones (P < 0.001). Sensitivity was 0.91 in specimens with VL of >1.0E6 IU/ml (95% CI 0.83 to 0.99) and decreased to 0.75 (95% CI 0.66 to 0.83) for specimens >1.0E3 IU/ml. Among symptomatic participants, the P-RDT displayed a sensitivity of 0.73 (95% CI 0.64 to 0.82), which peaked at 1.00 at 2 days post-onset of symptoms (DPOS) (95% CI 1.00 to 1.00), then decreased to 0.56 (95% CI 0.23 to 0.88) at 5 DPOS. There was a trend toward lower P-RDT sensitivity in symptomatic children <12 years (0.62 [95% CI 0.45 to 0.78]) versus ≥12 years (0.80 [95% CI 0.69 to 0.91]; P = 0.09). In asymptomatic participants, the P-RDT displayed a sensitivity of 0.43 (95% CI 0.26 to 0.61). Specificity was 1.00 in symptomatic and asymptomatic children (95% CI 0.99 to 1.00). The overall 73% and 43% sensitivities of P-RDT in symptomatic and asymptomatic children, respectively, was below the 80% cutoff recommended by the World Health Organization. We observed a correlation between VL and P-RDT sensitivity, as well as variation of sensitivity according to DPOS, a major determinant of VL. These data highlight the limitations of RDTs in children, with the potential exception in early symptomatic children ≥12yrs.

Sensitivity of nasopharyngeal, oropharyngeal, and nasal wash specimens for SARS-CoV-2 detection in the setting of sampling device shortage.

In the context of an unprecedented shortage of nasopharyngeal swabs (NPS) or sample transport media during the coronavirus disease 2019 (COVID-19) crisis, alternative methods for sample collection are needed. To address this need, we validated a cell culture medium as a viral transport medium, and compared the analytical sensitivity of SARS-CoV-2 RT-PCR in nasal wash (NW), oropharyngeal swab (OPS), and NPS specimens. Both the clinical and analytical sensitivity were comparable in these three sample types. OPS and NW specimens may therefore represent suitable alternatives to NPS for SARS-CoV-2 detection.

[SARS-CoV-2 screening in travelers: what approach to assess transmission risk ?] / Dépistage de l'infection à SARS-CoV-2 chez les voyageurs - Quelle approche pour évaluer le risque de transmis.

Before a trip, a screening for SARS-CoV-2 infection by RT-PCR is often required and raises the problem of detection of residual viral RNA at distance from the acute infection (post-Covid). At the University Hospital of Geneva, we developed an expertise to distinguish acute from post-Covid infections. Between October and December 2020, 30% of the people tested positive were able to travel because the result corresponded to post-Covid and 65% were put in isolation because of an acute infection with a risk of transmission. To overcome the detection of residual viral RNA by RT-PCR, a rapid antigenic test would be an interesting and less expensive alternative. It could also be performed a few hours before departure.

Avant un voyage, un dépistage de l'infection à SARS-CoV-2 par RT-PCR est souvent exigé et soulève le problème de la détection d'ARN viral résiduel chez une personne à distance de l'infection aiguë (post-Covid). Aux HUG, nous avons développé une expertise permettant de distinguer les infections aiguës des post-Covid. Entre octobre et décembre 2020, 30 % des personnes dépistées positives ont pu voyager car le résultat correspondait à des post-Covid et 65 % ont été mises en isolement en raison d'une infection aiguë avec risque de transmission. Pour pallier la détection de l'ARN viral résiduel par la RT-PCR, un test rapide antigénique serait une alternative intéressante et moins chère. Il pourrait également être effectué juste avant le départ.

Maladies infectieuses.

What's new in infectious diseases in 2020 ? This year has been marked by the COVID-19 pandemic, prompting a review of the current knowledge on SARS-CoV-2 and its management in this article. The results of the Swiss project «â€…PIRATE ¼ indicate non-inferiority between CRP-guided antibiotic durations or fixed 7-day durations and 14-day durations for Gram-negative bacteremia. A Mongolian study did not show any benefit of vitamin D substitution in protecting children from tuberculosis. Baloxavir, a new antiviral against the flu, has been approved by Swissmedic. Finally, new American recommendations for therapeutic monitoring of vancomycin and universal screening for hepatitis C virus have been published.

Que dire des nouveautés en maladies infectieuses en 2020 ? L'année a été marquée évidemment par la pandémie du Covid-19, motivant une revue dans cet article, des connaissances actuelles sur le SARS-CoV-2 et de sa prise en charge. Les résultats du projet suisse PIRATE ont montré une non-infériorité pour les bactériémies Gram négatif entre une antibiothérapie de 7 jours ou guidée par la CRP face à une durée de 14 jours. Une étude mongolienne n'a pas permis de montrer le bénéfice d'une substitution en vitamine D chez les enfants sur l'incidence de la tuberculose. Le baloxavir, un nouvel antiviral contre la grippe, a été approuvé par Swissmedic. Et enfin, des nouvelles recommandations américaines sur le monitoring thérapeutique de la vancomycine et sur le dépistage universel de l'hépatite C ont été publiées.

Inside the lungs of COVID-19 disease.

In the setting of the coronavirus disease 2019 (COVID-19) pandemic, only few data regarding lung pathology induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is available, especially without medical intervention interfering with the natural evolution of the disease. We present here the first case of forensic autopsy of a COVID-19 fatality occurring in a young woman, in the community. Diagnosis was made at necropsy and lung histology showed diffuse alveolar damage, edema, and interstitial pneumonia with a geographically heterogeneous pattern, mostly affecting the central part of the lungs. This death related to COVID-19 pathology highlights the heterogeneity and severity of central lung lesions after natural evolution of the disease.

Compartmentalization of a Multidrug-Resistant Cytomegalovirus UL54 Mutant in a Stem Cell Transplant Recipient with Encephalitis.

We report a case of cytomegalovirus encephalitis in a hematopoietic stem cell transplant recipient. A previously uncharacterized V787E mutation in UL54 was identified in cerebrospinal fluid but not plasma specimens. For the V787E recombinant virus, the half maximal effective concentrations for ganciclovir, foscarnet, and cidofovir were 8.6-, 3.4- and 2.9-fold higher than for wild-type virus, and the replicative capacity was lower. The introduction of a bulkier and negatively charged glutamate residue at position 787 could destabilize the finger domain of UL54 DNA polymerase. Viral genotyping of cerebrospinal fluid is warranted in subjects with cytomegalovirus encephalitis, owing to the low penetration of antivirals in this compartment.

Ebola Virus Shedding and Transmission: Review of Current Evidence.

BACKGROUND: The magnitude of the 2013-2016 Ebola virus disease outbreak in West Africa was unprecedented, with >28 500 reported cases and >11 000 deaths. Understanding the key elements of Ebola virus transmission is necessary to implement adequate infection prevention and control measures to protect healthcare workers and halt transmission in the community. METHODS: We performed an extensive PubMed literature review encompassing the period from discovery of Ebola virus, in 1976, until 1 June 2016 to evaluate the evidence on modes of Ebola virus shedding and transmission. FINDINGS: Ebola virus has been isolated by cell culture from blood, saliva, urine, aqueous humor, semen, and breast milk from infected or convalescent patients. Ebola virus RNA has been noted in the following body fluids days or months after onset of illness: saliva (22 days), conjunctiva/tears (28 days), stool (29 days), vaginal fluid (33 days), sweat (44 days), urine (64 days), amniotic fluid (38 days), aqueous humor (101 days), cerebrospinal fluid (9 months), breast milk (16 months [preliminary data]), and semen (18 months). Nevertheless, the only documented cases of secondary transmission from recovered patients have been through sexual transmission. We did not find strong evidence supporting respiratory or fomite-associated transmission.

Zika virus: practical guidelines. / Virus Zika : recommandations pratiques.

Zika virus suddenly emerged in Latin America in 2015­2016. Congenital malformations have been observed in infected pregnant women, causing a major public health impact in affected countries, particularly in Brazil. In addition, sexual transmission of Zika virus has been well documented. This led to the development of prevention strategies and recommendations for travellers visiting at risk countries. These documents are regularly amended depending on the evolution of scientific knowledge, the epidemiologic trends and the national and international guidelines. Through practical cases, we present here the guidelines developed by the Geneva University Hospitals.

Le virus Zika a émergé brusquement en 2015­2016 en Amérique latine. Lors de cette épidémie, des complications fœtales ont pu être observées avec des conséquences majeures sur la santé publique de ces pays, en particulier au Brésil. De plus, une transmission par voie sexuelle du virus a été bien documentée. Il a ainsi été nécessaire de développer des stratégies de prévention et des recommandations pour les voyageurs visitant des pays à risque. Ces documents sont évolutifs en fonction des connaissances scientifiques, de l'épidémiologie de la maladie et des recommandations nationales et internationales. Par l'intermédiaire de cas illustratifs, nous présentons les recommandations utilisées aux Hôpitaux universitaires de Genève.

Astrovirus MLB2, a New Gastroenteric Virus Associated with Meningitis and Disseminated Infection.

Next-generation sequencing has identified novel astroviruses for which a pathogenic role is not clearly defined. We identified astrovirus MLB2 infection in an immunocompetent case-patient and an immunocompromised patient who experienced diverse clinical manifestations, notably, meningitis and disseminated infection. The initial case-patient was identified by next-generation sequencing, which revealed astrovirus MLB2 RNA in cerebrospinal fluid, plasma, urine, and anal swab specimens. We then used specific real-time reverse transcription PCR to screen 943 fecal and 424 cerebrospinal fluid samples from hospitalized patients and identified a second case of meningitis, with positive results for the agent in the patient's feces and plasma. This screening revealed 5 additional positive fecal samples: 1 from an infant with acute diarrhea and 4 from children who had received transplants. Our findings demonstrate that astrovirus MLB2, which is highly prevalent in feces, can disseminate outside the digestive tract and is an unrecognized cause of central nervous system infection.

Chimeric rhinoviruses obtained via genetic engineering or artificially induced recombination are viable only if the polyprotein coding sequence derives from the same species.

UNLABELLED: Recombination is a widespread phenomenon that ensures both the stability and variation of RNA viruses. This phenomenon occurs with different frequencies within species of the Enterovirus genus. Intraspecies recombination is described frequently among non-rhinovirus enteroviruses but appears to be sporadic in rhinoviruses. Interspecies recombination is even rarer for rhinoviruses and mostly is related to ancient events which contributed to the speciation of these viruses. We reported that artificially engineered 5' untranslated region (UTR) interspecies rhinovirus/rhinovirus or rhinovirus/non-rhinovirus enterovirus recombinants are fully viable. Using a similar approach, we demonstrated in this study that exchanges of the P1-2A polyprotein region between members of the same rhinovirus species, but not between members of different species, give rise to competent chimeras. To further assess the rhinovirus intra- and interspecies recombination potential, we used artificially induced recombination by cotransfection of 5'-end-deleted and 3'-end-deleted and replication-deficient genomes. In this system, intraspecies recombination also resulted in viable viruses with high frequency, whereas no interspecies rhinovirus recombinants could be recovered. Mapping intraspecies recombination sites within the polyprotein highlighted recombinant hotspots in nonstructural genes and at gene boundaries. Notably, all recombinants occurring at gene junctions presented in-frame sequence duplications, whereas most intragenic recombinants were homologous. Taken together, our results suggest that only intraspecies recombination gives rise to viable rhinovirus chimeras in the polyprotein coding region and that recombination hotspots map to nonstructural genes with in-frame duplications at gene boundaries. These data provide new insights regarding the mechanism and limitations of rhinovirus recombination. IMPORTANCE: Recombination represents a means to ensure both the stability and the variation of RNA viruses. While intraspecies recombination is described frequently among non-rhinovirus enteroviruses, it seems to occur more rarely in rhinoviruses. Interspecies recombination is even rarer in this virus group and is mostly related to ancient events, which contributed to its speciation. We used engineered chimeric genomes and artificially induced RNA recombination to study experimentally the recombination potential of rhinoviruses and analyze recombination sites. Our results suggest that only intraspecies recombination gives rise to viable chimeras in the polyprotein coding region. Furthermore, characterization of intraspecies chimeras provides new insight into putative recombination hotspots within the polyprotein. In summary, we applied two powerful and complementary experimental approaches to improve current knowledge on rhinovirus recombination.

E119D Neuraminidase Mutation Conferring Pan-Resistance to Neuraminidase Inhibitors in an A(H1N1)pdm09 Isolate From a Stem-Cell Transplant Recipient.

BACKGROUND: An influenza A(H1N1)pdm09 infection was diagnosed in a hematopoietic stem cell transplant recipient during conditioning regimen. He was treated with oral oseltamivir, later combined with intravenous zanamivir. The H275Y neuraminidase (NA) mutation was first detected, and an E119D NA mutation was identified during zanamivir therapy. METHODS: Recombinant wild-type (WT) E119D and E119D/H275Y A(H1N1)pdm09 NA variants were generated by reverse genetics. Susceptibility to NA inhibitors (NAIs) was evaluated with a fluorometric assay using the 2'-(4-methylumbelliferyl)-α-D-N-acetylneuraminic acid (MUNANA) substrate. Susceptibility to favipiravir (T-705) was assessed using plaque reduction assays. The NA affinity and velocity values were determined with NA enzymatic studies. RESULTS: We identified an influenza A(H1N1)pdm09 E119D mutant that exhibited a marked increase in the 50% inhibitory concentrations against all tested NAIs (827-, 25-, 286-, and 702-fold for zanamivir, oseltamivir, peramivir, and laninamivir, respectively). The double E119D/H275Y mutation further increased oseltamivir and peramivir 50% inhibitory concentrations by 790- and >5000-fold, respectively, compared with the WT. The mutant viruses remained susceptible to favipiravir. The NA affinity and velocity values of the E119D variant decreased by 8.1-fold and 4.5-fold, respectively, compared with the WT. CONCLUSIONS: The actual emergence of a single NA mutation conferring pan-NAI resistance in the clinical setting reinforces the pressing need to develop new anti-influenza strategies.

[Zika virus : a review]. / Virus Zika : mise au point.

Since early 2015, the Zika virus epidemic has spread rapidly through South America and the Caribbean and the first cases of local transmission have just been reported in Florida. Maternal infection during pregnancy can cause serious birth defects. Pregnant women and their partners should avoid travelling to areas of Zika epidemic.

Depuis le début de l'année 2015, l'épidémie de virus Zika s'est répandue rapidement en Amérique du Sud et dans les Caraïbes et récemment les premiers cas de transmission autochtone ont été déclarés en Floride. Une infection maternelle au cours de la grossesse peut être responsable de graves malformations fœtales. Le voyage dans les zones d'épidémie est déconseillé aux femmes enceintes et à leur partenaire.

[Varicella Zoster infections in adults: beyond shingles?]. / Infection par le virus Varicella zoster chez l'adulte: au-delà du zona?

Chickenpox is a generally benign condition during childhood, but it can cause severe complications when affecting teenage or adult patients. Immunodeficiency and pregnancy are risk factors for disseminated disease with pulmonary, neurological and/or hepatic involvement. Reinfection may be more frequent than previously thought, and management is identical to that of primary infection. The most common manifestation of viral reactivation is shingles, but it can also cause meningitis and vasculopathy, as well as disseminated herpes zoster in the immunocompromised patient. In this article, we will review the clinical manifestations and management of VZV infection in adults.