Differences and similarities between Monkeypox and Chickenpox in children during an outbreak.

INTRODUCTION: Herein, we described cases of children under 16 years old suspected to be infected with Monkeypox virus (MKPV) and diagnosed with chickenpox in public hospitals of Marseille, south of France. MATERIAL AND METHODS: We conducted a retrospective study from March 23rd, 2022 to October 20th, 2022 in our institution of results of MKPV DNA and varicella-zoster virus (VZV) DNA detection by PCR performed on cutaneous lesions swabs collected from children <16 years old. RESULTS: None of the cutaneous swabs collected from 14 children were positive for MKPV DNA. In contrast, 30/168 (17 %) cutaneous swabs collected from children were positive for VZV DNA. Of these 30 VZV-positive children, 7 had been suspected of MKPV infection because of their atypical rash, due to the location of the lesions and the chronology of their appearance. DISCUSSION: As in our cohort, pediatric cases of the 2022 Monkeypox outbreak in non-endemic developed countries have been very rare. This variant of MKPV does not normally spread easily and requires very close physical contact between an infected person (skin lesions, bodily fluids or respiratory droplets) and another person to be transmitted. It will nevertheless be a question of remaining vigilant as not to ignore the possibility of close contact or sexual transmission of Monkeypox in a child, or the possibility of a new and more contagious variant. CONCLUSION: It is difficult to differentiate Monkeypox infection from other infections associated with rashes, it is important to remember that viruses change as well as their forms of presentation.

Outbreak of adenovirus D8 in a neonatal intensive care unit involving multiple simultaneous transmission pathways.

BACKGROUND: Adenovirus (ADV) outbreaks in neonatal intensive care units (NICU) can lead to durable transmission and serious adverse outcomes. This study describes the investigation and control of an ADV-D8 outbreak in an NICU, associated with ophthalmologic equipment used during retinopathy of prematurity (ROP) screening. Cases were observed in neonates, parents and nurses. METHODS: The outbreak investigation was performed including sampling patients, parents and health care workers as well as the environment for molecular detection of ADV DNA. The investigation was also conducted in the guest house where some parents were temporary residents. A retrospective cohort study focused on neonates hospitalized during the epidemic period to assess the risk associated with ROP examination. RESULTS: Fifteen cases were identified in neonates; all but one presented with conjunctivitis. Two healthcare workers and 18 parents acquired conjunctivitis. ADV DNA was identified on the RetCam and on the freezer shared by parents. All ADV-positive samples were typed as ADV-D8. ADV infections occurred more frequently in neonates who had ROP examinations (37.8% (14/37) vs (0.9% (1/110); P<0.001) (relative risk 41.6; (5.7-305.8)). The RetCam was disinfected between two examinations using a disinfectant that was virucidal on ADV after a 30-min contact. CONCLUSION: This outbreak was significantly associated with ROP examination with a RetCam that had a disinfection protocol ill-adapted to rapid patient turnover. In addition, nosocomial transmission via the parents to neonates and parent-to-parent transmission is likely to have played a role in the dissemination of cases. No further cases were observed after the new disinfection procedure was enforced.

Afebrile meningoencephalitis with transient central facial paralysis due to Toscana virus infection, southeastern France, 2014 [corrected].

We report a case of meningoencephalitis caused by Toscana virus (TOSV) with central facial paralysis lasting over two days acquired in south-eastern France. The patient was not febrile either before or during the course of the disease. The diagnosis was established by both real-time RT-PCR and virus isolation with complete genome sequencing. This case emphasises the need to consider TOSV in non-febrile neurological syndromes in people living in or having travelled to the Mediterranean area.

Outbreak of adenovirus type 1 severe pneumonia in a French intensive care unit, September-October 2012.

We herein describe and analyse the first outbreak of severe pneumonia caused by human adenovirus type1 (HAdV C type 1), which included immunocompetent patients in an intensive care unit (ICU) of Marseille, France, and occurred between September and October 2012. Seven successive patients were diagnosed by HAdV specific real-time polymerase chain reaction with a positive bronchoalveolar lavage. After the collection of nasopharyngeal swabs from healthcare workers, three nurses working night shifts tested positive for HAdV C including one that had exhibited respiratory signs while working one week before the outbreak. She was the most likely source of the outbreak. Our findings suggest that HAdV-1 could be considered as a possible cause of severe pneumonia even in immunocompetent patients with a potential to cause outbreaks in ICUs. HAdV rapid identification and typing is needed to curtail the spread of this pathogen. Reinforcing hand hygiene with antiseptics with demonstrated activity against non-enveloped viruses and ensuring that HCWs with febrile respiratory symptoms avoid direct patient contact are critical measures to prevent transmission of HAdV in healthcare settings.

Toscana virus infections: a case series from France.

Toscana virus (TOSV) is a neglected sandfly-borne pathogen in Mediterranean countries. Although discovered four decades ago, articles that describe the clinical aspects are scarce and consist mostly of case reports, with few series of cases. We studied retrospectively symptomatic TOSV infections in patients hospitalized in Marseille (France) from 2004 to 2011. Seventeen patients were classified as probable or confirmed cases. Fourteen cases (82%) occurred between June and September, and 3 cases in March, April and November. Two cases were potentially imported from Croatia and Tuscany. All patients presented with fever and neurological signs were observed such as aseptic meningitis (n = 6), muscular symptoms (n = 3), or encephalitis (n = 4). The outcome was always favorable. At the acute stage, anti TOSV IgM were observed in 14/17 patients, neutralization tests were positive for 3/8 patients, and RT-PCR confirmed TOSV infections in 5/8 CSF specimens.

Increased incidence of acute parvovirus B19 infections in Marseille, France, in 2012 compared with the 2002-2011 period.

Human parvovirus B19 occurs worldwide and causes mild or asymptomatic disease in the form of cyclic local epidemics usually occurring in late winter and early summer. In 2012, a dramatic increase in cases was observed in the Public hospitals system of Marseille, with a total of 53 cases reported. Here, we describe the characteristics of this outbreak and compare it with the local epidemiology of B19V infections observed during the 2002-2011 period.

Fulminant Hepatitis Due to Father-to-Newborn Transmission of Herpes Simplex Virus type 1.

We describe a case of a severe neonatal infection by herpes simplex virus (HSV) type 1 acquired postnatally from his father. The delivery and the first days of life were normal. He developed liver failure and disseminated intravascular coagulation when he was 19 days old. He was treated with intravenous acyclovir and the outcome was favorable. This case underlines that prevention of post-natal transmission of HSV merits to be considered in educational pregnancy programs directed at mothers and fathers.

Lack of nasal carriage of novel corona virus (HCoV-EMC) in French Hajj pilgrims returning from the Hajj 2012, despite a high rate of respiratory symptoms.

A cohort of 154 French Hajj pilgrims participating in the 2012 Hajj were systematically sampled with nasal swabs prior to returning to France, and screened for the novel HCoV-EMC coronavirus by two real-time RT-PCR assays. Despite a high rate of respiratory symptoms (83.4%), including 41.0% influenza-like illness, no case of HCoV-EMC infection was detected. Despite the fact that zoonotic transmission was suspected in the first few cases, a recent family cluster in the Kingdom of Saudi Arabia suggests that the virus might show at least limited spread from person to person, which justifies continuing epidemiological surveillance.

2012 outbreak of acute haemorrhagic conjunctivitis in Indian Ocean Islands: identification of Coxsackievirus A24 in a returned traveller.

In May 2012, a Coxsackievirus A24 haemorrhagic conjunctivitis was diagnosed in Marseille, France, in a traveller returning from the Comoros Islands. This case allowed identification of the cause of an ongoing outbreak of haemorrhagic conjunctivitis in Indian Ocean Islands, illustrating that returning travellers may serve as sentinels for infectious diseases outbreaks in tropical areas where laboratory investigation is limited.

Evaluation of the Xpert Flu test and comparison with in-house real-time RT-PCR assays for detection of influenza virus from 2008 to 2011 in Marseille, France.

Rapid documentation of respiratory specimens can have an impact on the management of patients and their relatives in terms of preventive and curative measures. We compared the results of the Xpert(®) Flu assay (Cepheid) with three real-time RT-PCR assays using 127 nasopharyngeal samples, of which 75 were positive for influenza A (with 52 identified as A/H1N1-2009) and 52 were positive for influenza B. The Xpert(®) Flu assay presented a quasi-absence of non-interpretable tests, and showed sensitivity and specificity of 100% and 100% for Flu A, 98.4% and 100% for A/H1N1-2009, and 80.7% and 100% for Flu B.

Screening and detection of human enterovirus 71 infection by a real-time RT-PCR assay in Marseille, France, 2009-2011.

Enterovirus-positive samples diagnosed in Marseille (January 2009 to September 2011) were screened for EV71 by real-time RT-PCR. EV71 was detected in three children below the age of 2 years with no history of overseas travel; two of these cases were associated with severe clinical presentation. Viruses demonstrated genetic similarity to other European genogroup C2 strains. Strain MRS/09/3663 complete sequencing revealed 97.6% identity across the entire genome with a 2008 Singapore isolate, without signs of possible recombination events. To our knowledge, this is the first detection of EV71 infection in Marseille, France, that confirms the current circulation of EV71 in France.

Serological study of the 2009 pandemic due to influenza A H1N1 in the metropolitan French population.

We looked for evidence of antibodies to the 2009 influenza A/H1N1 pandemic virus in panels of sera from individuals living in metropolitan France, obtained either before, during or after the epidemic, using standard haemagglutination inhibition and microneutralization tests. The difference between seroprevalence values measured in post- and pre-epidemic panels was used as an estimate of seroconversion rate in different age groups (23.4% (0-24 years, age-group 0); 16.5% (25-34); 7.9% (35-44); 7.2% (45-54); 1.6% (55-64); and 3.1% (>65)), confirming that the distribution of cases in different age groups was similar to that of the seasonal H1N1 virus. During the pre-pandemic period low-titre cross-reactive antibodies were present in a large proportion of the population (presumably acquired against seasonal H1N1) whereas cross-reactive antibodies were detected in individuals over the age of 65 years with significantly higher prevalence and serological titres (presumably acquired previously against Spanish flu-related H1N1 strains). Clinical data and analysis of post-pandemic seroprevalence showed that few of these latter patients were infected by the influenza virus during the epidemic. In contrast, the majority of both clinical cases and seroconversions were recorded in the 0-24 age group and a global inverse relationship between prevalence of antibodies to pH1N1 in the pre-pandemic period and rate of seroconversion was observed amongst age groups. Our results emphasize the complex relationships involved in antigenic reactivity to pandemic and seasonal H1N1 viral antigens; hence the difficulty in distinguishing between low-titre specific and cross-reactive antibodies, establishing precise seroprevalence numbers and fully understanding the relationship between previous immunity to seasonal viruses and protection against the novel variant.

Comparative detection of enterovirus RNA in cerebrospinal fluid: GeneXpert system vs. real-time RT-PCR assay.

Enteroviruses (EVs) constitute the most common cause of aseptic meningitis in both children and adults. Molecular techniques have now been recognized as the reference standard for the diagnosis of EV infections, and the rapidity of the molecular diagnosis of EV meningitis has been shown to be a determining factor in the management of patients. The rapid documentation of EV RNA in cerebrospinal fluid (CSF) is key to adapting patient management and the therapeutic regimen. To shorten the time needed for virological documentation, we implemented EV RNA detection in two point-of-care (POC) laboratories. Here, we present the results of the POC detection of EV RNA with the Xpert EV kit on the GeneXpert integrated system, and a comparison with the real-time RT-PCR (rtRT-PCR) assay routinely used in the core virology laboratory. From January to September 2009, a total of 310 CSF samples were tested. The rtRT-PCR gave 81 positive, 225 negative and four 'indeterminate' results. POC results were concordant in 81.6% (253/310). Most of the discrepancies consisted of 'indeterminate' results at the POC level (16%). Calculated performances (excluding the indeterminate results) of the Xpert EV kit on the GeneXpert system in POC settings were 100%, 98.9%, 97.6% and 100% for Sensibility, Specificity, positive predictive value and negative predictive value, respectively. Taken together, these results indicate that the implementation of POC detection of EV RNA can provide robust results in <4 h, and may have a significant impact on patient management, therapeutic attitude, and hospitalization costs.

Fatal case of Reye's syndrome associated with H3N2 influenza virus infection and salicylate intake in a 12-year-old patient.

We describe a fatal case of Reye's syndrome in a 12-year-old male patient during an influenza A (H3N2) infection for which he received salicylates. In the current situation of the novel A/H1N1 virus pandemic, we believe that it is of high importance to emphasize the risks associated with salicylate intake to avoid the reappearance of Reye's syndrome.

Cytomegalovirus risk factors in renal transplantation with modern immunosuppression.

BACKGROUND: Immunosuppressive regimens have lowered the rate of kidney rejection, but with increasing immunodeficiency-related complications. New cytomegalovirus (CMV) prophylaxis also has become available. The impact of these 2 developments on CMV diseases has not been well evaluated. We conducted a randomized trial comparing a drug regimen common in the 1980s, cyclosporin A (CsA) with azathioprine (Aza), with a drug combination used most today, tacrolimus (Tac) with mycophenolate mofetil (MMF), and we analyzed CMV risk factors in kidney transplant patients. METHODS: The 300 patients included in the trial underwent the same universal prophylaxis and preemptive therapy. CMV events and risk factors were prospectively recorded. RESULTS: With preventive and preemptive strategies combined for 3 months, CMV replication was detected in 32.6% and CMV disease in 18.1% of patients. Multivariate analysis on risk factors for CMV disease were CMV donor (D)/recipient (R) matching and first month renal function (risk ratio [95% confidence interval]: 1.02 [1.01; 1.04]; P=0.011), but not the immunosuppressive regimen (P=0.35). The D+/R- combination increased the risk of CMV disease by a factor of 9 (P<0.0001) when compared with D-/R- status, and a factor of 3.5 (P<0.0001) when compared with all CMV-positive recipients. Despite the 50% rate of CMV disease in the D+/R- group, no asymptomatic CMV replication was detected with the preemptive strategy. CONCLUSIONS: With modern immunosuppression, a sequential quadritherapy with Tac/MMF, and a 3-month CMV prevention strategy, the risk for CMV disease remains close to that with CsA/Aza. A CMV-negative recipient transplanted from a CMV-positive donor (D+/R-) remains a major risk factor, calling for better CMV prophylaxis or matching in negative recipients. Preemptive strategy thus appeared inefficient for this high-risk group. Transplant recipients with altered renal function should also be considered at risk.

Interim report on the A/H1N1 influenza virus pandemic in Marseille, France, April-November 2009.

We report here the results of a 7-month survey of the influenza A/H1N1 pandemic in the Virology laboratory of the public hospitals of Marseille (April-November 2009). In total, 8 587 samples were analysed during this period, of which 1 974 (23%) were positive for the novel influenza variant. The analysis of results obtained using rapid influenza diagnostic tests (RIDTs) revealed a global sensitivity of 49.4% (vs. molecular qRT-PCR detection), strongly correlated with age groups (varying from 30% to 58% for patients >40 age and <10, respectively), indicating that RIDTs can be helpful in accelerating the management of suspected cases. Epidemiological analysis showed that the winter influenza wave began in October in Marseille (i.e. 2 to 3 months earlier than usual seasonal influenza outbreaks) and that the majority of autochthonous cases were observed in patients younger than 20 years old, with a low number of cases in patients over 60 years old. In November 2009, 22.2% (167/754) of patients with a laboratory diagnosis of influenza A/H1N1 infection were hospitalized, of which 9% (15/167) were admitted to an intensive care unit (ICU). Patients in the extreme age groups (>40 years old and <1) were significantly more often hospitalized than others, and 2.4% of hospitalized patients died. During the last 3 weeks of the period, the average number of bed-days attributable to H1N1sw-positive patients was 31.4, of which 5.9 were in ICUs.

Impact of diagnostic procedures on patient management and hospitalization cost during the 2000 and 2005 enterovirus epidemics in Marseilles, France.

Enteroviruses are frequent aetiological agents of central nervous system infections in humans. In 2000 and 2005, two large outbreaks of Echovirus 30 (a member of species human enterovirus B) were observed in the University Hospitals of Marseilles (France). Between the two epidemics, the diagnostic protocols for enterovirus infection were modified, moving from viral cultures and classic RT-PCR in 2000 to real-time RT-PCR in 2005. We compared some viral and epidemiological characteristics of the 2000 and 2005 outbreaks with special attention to diagnostic procedures and to the subsequent clinical management of patients. Despite similar virological and epidemiological characteristics during both outbreaks, our results show that real-time RT-PCR techniques used in 2005 noticeably shortened the period of time necessary to deliver diagnostic results and suggest that this was associated with a decrease in the duration of hospitalization for positive cases. In conclusion, this study suggests that the improvement of enterovirus diagnosis had a major financial impact on the management of the 2005 epidemic in Marseilles and may constitute an interesting example of how new diagnostic methods in microbiology can be self-financed through improvement in patient management.