Publications by authors named "Judith M Hübschen"

60 Publications

Comprehensive surveillance data suggest a prominent role of parvovirus B19 infection in Belarus and the presence of a third subtype within subgenotype 1a.

Sci Rep 2021 Jan 13;11(1):1225. Epub 2021 Jan 13.

Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg.

Human parvovirus B19 (B19V) infection is not notifiable in Belarus and its most common clinical presentation erythema infectiosum (EI) is often difficult to distinguish from other exanthematous diseases. The objective of this study was to provide comprehensive data about EI epidemiology in Belarus based on the serological and molecular investigation of samples from measles and rubella discarded cases collected between 2005 and 2019. Overall, 4919 sera were investigated for IgM antibodies against B19V and the positive cases were analysed according to year, season and age. B19V DNA was amplified by PCR in a total of 238 sera from all over the country, and sequenced for phylogenetic analyses. B19V infection was confirmed in 1377 (27.8%) measles and rubella discarded cases. Two high incidence periods and a seasonal increase of EI between mid-February to mid-July were identified. Children from 4 to 6 and from 7 to 10 years of age represented the largest groups of patients (22.51% and 22.66% of all cases, respectively), followed by adults between 20 and 29 years of age (14.23%). Among the 238 B19Vs sequenced, one belonged to subgenotype 3b and 237 to subgenotype 1a with 81 (34.2%) clustering with subtypes 1a1 and 153 (64.6%) with 1a2. Three strains (1.2%) formed an additional, well-supported cluster suggesting the presence of another subtype of 1a, tentatively named 1a3. The epidemiological and molecular analyses highlighted not only the prominent role of B19V in exanthematous diseases in Belarus, but also suggested a previously underestimated diversity of subgenotype 1a sequences with a third subtype 1a3.
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http://dx.doi.org/10.1038/s41598-020-79587-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7807032PMC
January 2021

High seroprevalence of Foot and Mouth Disease in Laos: Call for nationwide vaccination campaigns and disease surveillance.

Transbound Emerg Dis 2020 Oct 28. Epub 2020 Oct 28.

Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg.

Foot and mouth disease (FMD) virus remains enzootic in Lao People's Democratic Republic (Lao PDR) due to insufficient control measures, including low vaccination coverage. We assessed virus epidemiology and evaluated knowledge, attitude and practice of Lao farmers and animal health stakeholders towards FMD to support politics in devising evidence-based control measures. Sera were collected from 972 domestic ruminants in three provinces of Lao PDR: Vientiane Capital, Vientiane and Xiengkhouang provinces. Seroprevalence of antibodies directed against non-structural proteins of FMD virus was assessed using a commercial ELISA. Positive sera were further characterized by detecting antibodies directed against the structural proteins of FMD serotypes O, A and Asia 1. Information about farm management, biosecurity practices, livestock trade, and past FMD outbreaks was obtained. Overall 35% (340/972) of the ruminants had antibodies against FMD virus with a similar seroprevalence in each province. Seroprevalence depended significantly on the ruminant species (p < .001): 61% of buffaloes, but only 41% of cattle and 15% of goats were seropositive. While antibodies against FMD serotype Asia 1 were absent, 87% (297/340) of the seropositive animals had antibodies against FMD serotype O and 32% (110/340) against FMD serotype A. Many seropositive animals (31%) had antibodies against both serotypes O and A. The majority of the farmers could name the symptoms of FMD and the susceptible animal species. Although many had likely observed FMD outbreaks in their herd and were aware of FMD vaccines, only few vaccinated their animals. This study confirms that FMD remains enzootic in at least three provinces of Lao PDR where vaccination coverage is low. It also shows the relevance of nationwide active and passive disease surveillance, as well as of vaccination campaigns using bivalent FMD vaccines and targeting all susceptible animal species.
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http://dx.doi.org/10.1111/tbed.13895DOI Listing
October 2020

Challenges to Achieving Measles Elimination, Georgia, 2013-2018.

Emerg Infect Dis 2020 11;26(11):2565-2577

Controlling measles outbreaks in the country of Georgia and throughout Europe is crucial for achieving the measles elimination goal for the World Health Organization's European Region. However, large-scale measles outbreaks occurred in Georgia during 2013-2015 and 2017-2018. The epidemiology of these outbreaks indicates widespread circulation and genetic diversity of measles viruses and reveals persistent gaps in population immunity across a wide age range that have not been sufficiently addressed thus far. Historic problems and recent challenges with the immunization program contributed to outbreaks. Addressing population susceptibility across all age groups is needed urgently. However, conducting large-scale mass immunization campaigns under the current health system is not feasible, so more selective response strategies are being implemented. Lessons from the measles outbreaks in Georgia could be useful for other countries that have immunization programs facing challenges related to health-system transitions and the presence of age cohorts with historically low immunization coverage.
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http://dx.doi.org/10.3201/eid2611.200259DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7588556PMC
November 2020

Emerging Influenza D virus infection in European livestock as determined in serology studies: Are we underestimating its spread over the continent?

Transbound Emerg Dis 2020 Sep 1. Epub 2020 Sep 1.

IHAP, Université de Toulouse, INRAE, ENVT, Toulouse, France.

Influenza D virus (IDV) is a novel orthomyxovirus that was first isolated in 2011 in the United States from a swine exhibiting influenza-like disease. To date, its detection is extended to all continents and in a broad host range: IDV is circulating in cattle, swine, feral swine, camelids, small ruminants and horses. Evidence also suggests a possible species jump to humans, underlining the issue of zoonotic potential. In Europe, serological investigations in cattle have partially allowed the understanding of the virus diffusion in different countries such as Italy, France, Luxembourg and Ireland. The infection is widespread in cattle but limited in other investigated species, consolidating the assumption of cattle as IDV primary host. We hypothesize that commercial livestock trade could play a role in the observed differences in IDV seroprevalence among these areas. Indeed, the overall level of exposure in cattle and swine in destination countries (e.g. Italy) is higher than in origin countries (e.g. France), leading to the hypothesis of a viral shedding following the transportation of young cattle abroad and thus contributing to larger diffusion at countries of destination. IDV large geographic circulation in cattle from Northern to more Southern European countries also supports the hypothesis of a viral spread through livestock trade. This review summarizes available data on IDV seroprevalence in Europe collected so far and integrates unpublished data from IDV European surveillance framework of the last decade. In addition, the possible role of livestock trade and biosecurity measures in this pathogen's spread is discussed.
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http://dx.doi.org/10.1111/tbed.13812DOI Listing
September 2020

Pluripotent Stem Cell-Based Models: A Peephole into Virus Infections during Early Pregnancy.

Cells 2020 02 26;9(3). Epub 2020 Feb 26.

Infectious Diseases Research Unit, Department of Infection and Immunity, Luxembourg Institute of Health, 4354 Esch-sur-Alzette, Luxembourg.

The rubella virus (RV) was the first virus shown to be teratogenic in humans. The wealth of data on the clinical symptoms associated with congenital rubella syndrome is in stark contrast to an incomplete understanding of the forces leading to the teratogenic alterations in humans. This applies not only to RV, but also to congenital viral infections in general and includes (1) the mode of vertical transmission, even at early gestation, (2) the possible involvement of inflammation as a consequence of an activated innate immune response, and (3) the underlying molecular and cellular alterations. With the progress made in the development of pluripotent stem cell-based models including organoids and embryoids, it is now possible to assess congenital virus infections on a mechanistic level. Moreover, antiviral treatment options can be validated, and newly emerging viruses with a potential impact on human embryonal development, such as that recently reflected by the Zika virus (ZIKV), can be characterized. Here, we discuss human cytomegalovirus (HCMV) and ZIKV in comparison to RV as viruses with well-known congenital pathologies and highlight their analysis on current models for the early phase of human development. This includes the implications of their genetic variability and, as such, virus strain-specific properties for their use as archetype models for congenital virus infections. In this review, we will discuss the use of induced pluripotent stem cells (iPSC) and derived organoid systems for the study of congenital virus infections with a focus on their prominent aetiologies, HCMV, ZIKV, and RV. Their assessment on these models will provide valuable information on how human development is impaired by virus infections; it will also add new insights into the normal progression of human development through the analysis of developmental pathways in the context of virus-induced alterations. These are exciting perspectives for both developmental biology and congenital virology.
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http://dx.doi.org/10.3390/cells9030542DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7140399PMC
February 2020

Serological evidence of swine exposure to pandemic H1N1/2009 influenza A virus in Burkina Faso.

Vet Microbiol 2020 Feb 31;241:108572. Epub 2019 Dec 31.

Infectious Diseases Research Unit, Department of Infection and Immunity, Luxembourg Institute of Health (LIH), 29 rue Henri Koch, L-4354, Esch-sur-Alzette, Luxembourg. Electronic address:

Despite improvement of human and avian influenza surveillance, swine influenza surveillance in sub-Saharan Africa is scarce and pandemic preparedness is still deemed inadequate, including in Burkina Faso. This cross-sectional study therefore aimed to investigate the (past) exposure of pigs to influenza A viruses. Practices of people with occupational contacts with pigs and their knowledge on influenza A were investigated in order to formulate future prevention guidelines. In 2016-2017, pig nasopharyngeal swabs and sera were collected and screened for the presence of influenza virus by RT-PCR or of anti-influenza antibodies by competitive ELISA. Seropositive samples were further characterized in virus microneutralization assays against human and swine H1N1 virus strains. Nasopharyngeal swabs were obtained from people with occupational contact with pigs and screened similarly. Demographic data as well as practices related to their profession were recorded. No influenza A virus was detected in nasopharyngeal swabs in humans (n = 358) or in pigs (n = 600). Seroprevalence in pigs reached 6.8 % (41/600) and seropositive animals were found in 50.0 % of extensive settings (10/20) and 19.0 % of (semi-)intensive farms (4/21). All positive sera reacted against the pandemic H1N1/2009 strain, while seropositivity against two Eurasian avian-like and one American swine H1N1 strains and individual titers were lower. These results suggested exposure to pandemic H1N1/2009 virus and cross-reactivity to other H1N1 strains. Farmers with higher frequency of contact to pigs, absence of protective equipment and lack of knowledge on zoonoses are likely key players in driving human-to-swine virus transmission.
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http://dx.doi.org/10.1016/j.vetmic.2019.108572DOI Listing
February 2020

Seroprevalence of measles, mumps, and rubella and genetic characterization of mumps virus in Khartoum, Sudan.

Int J Infect Dis 2020 Feb 20;91:87-93. Epub 2019 Nov 20.

Infectious Diseases Research Unit, Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg. Electronic address:

Background: In Sudan, neither mumps nor rubella vaccines are currently used and comprehensive data on the seroepidemiology of measles, mumps, and rubella (M.M.R), as well as information about circulating mumps virus genotypes, are lacking.

Methods: In 2015/2016, dried blood spot samples were collected from 294 children, 153 adults from the general population, and 241 healthcare workers (HCWs) from Khartoum. The samples were investigated for M.M.R IgG antibodies using ELISA. Oral fluid samples from 16 clinical mumps cases collected in 2017 were characterized by RT-PCR and sequencing.

Results: The seroprevalence of M.M.R antibodies among children was 93.5%, 63.6%, and 55.8%, while it was 93.5%, 90.8%, and 94.1% among adult volunteers and 99.2%, 97.1%, and 97.9% among HCWs. A high measles seroprevalence was observed among all children age groups, suggesting an effective control programme, while the mumps and rubella seroprevalence increased significantly with age (p<0.001), documenting active wild-type circulation. Our results demonstrated higher M.M.R seropositivity rates and IgG titres in HCWs compared to adult volunteers. Phylogenetic analysis showed the presence of genotype C mumps virus for the first time in Sudan.

Conclusions: The study findings provided new information on M.M.R epidemiology in Sudan, which may guide future control programmes in the country.
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http://dx.doi.org/10.1016/j.ijid.2019.11.019DOI Listing
February 2020

Vaccination of healthcare personnel in Europe: Update to current policies.

Vaccine 2019 12 14;37(52):7576-7584. Epub 2019 Oct 14.

Director, Mayo Vaccine Research Group, Mayo Clinic, Rochester, MN, United States.

We investigated and compared current national vaccination policies for health-care personnel (HCP) in Europe with results from our previous survey. Data from 36 European countries were collected using the same methodology as in 2011. National policies for HCP immunization were in place in all countries. There were significant differences in terms of number of vaccinations, target HCP and healthcare settings, and implementation regulations (recommended or mandatory vaccinations). Vaccination policies against hepatitis B and seasonal influenza were present in 35 countries each. Policies for vaccination of HCP against measles, mumps, rubella and varicella existed in 28, 24, 25 and 19 countries, respectively; and against tetanus, diphtheria, pertussis and poliomyelitis in 21, 20, 19, and 18 countries, respectively. Recommendations for hepatitis A immunization existed in 17 countries, and against meningococcus B, meningococcus C, meningococcus A, C, W, Y, and tuberculosis in 10, 8, 17, and 7 countries, respectively. Mandatory vaccination policies were found in 13 countries and were a pre-requisite for employment in ten. Comparing the vaccination programs of the 30 European countries that participated in the 2011 survey, we found that more countries had national vaccination policies against measles, mumps, rubella, hepatitis A, diphtheria, tetanus, poliomyelitis, pertussis, meningococcus C and/or meningococcus A, C, W, Y; and more of these implemented mandatory vaccination policies for HCP. In conclusion, European countries now have more comprehensive national vaccination programs for HCP, however there are still gaps. Given the recent large outbreaks of vaccine-preventable diseases in Europe and the occupational risk for HCP, vaccination policies need to be expanded and strengthened in several European countries. Overall, vaccination policies for HCP in Europe should be periodically re-evaluated in order to provide optimal protection against vaccine-preventable diseases and infection control within healthcare facilities for HCP and patients.
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http://dx.doi.org/10.1016/j.vaccine.2019.09.061DOI Listing
December 2019

Epidemiological, clinical and laboratory characteristics of the measles resurgence in the Republic of Serbia in 2014-2015.

PLoS One 2019 17;14(10):e0224009. Epub 2019 Oct 17.

WHO European Regional Reference Laboratory for Measles and Rubella, Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette and Laboratoire National de Santé, Dudelange, Luxembourg.

The Republic of Serbia is a country with ongoing endemic transmission of measles. The aim of this study is to summarize the main characteristics of the measles resurgence that occurred in Serbia in 2014-2015. The national surveillance data on measles was analysed in relation to the clinical, epidemiological and laboratory data. Between November 2014 and December 2015 a measles resurgence with 420 cases was observed in Serbia. Measles virus was initially introduced by and spread among citizens of Bosnia and Herzegovina with temporary residence in Serbia, before spreading to the resident population. Of the 223 patients with available medical records, 173 (77.6%) were unvaccinated. The overall measles incidence during the outbreak was 5.8/100.000. The highest age-specific incidence rate was recorded in children aged ≤4 years (25.9/100.000), but most cases (67.9%) were ≥20 years old. Hospitalization rate was high (32.9%) and included two cases of encephalitis associated with measles. In total, 42 health-care workers and 22 related cases including hospitalized patients (n = 13) contracted measles. The overall percentage of laboratory confirmed cases was 81.7% (n = 343/420). All measles virus sequences except one (D9) belonged to genotype D8, suggesting interruption of transmission after the previous outbreak in 2010-2011 caused by genotype D4 viruses. The growing number of adult patients as compared to previous epidemics, suggests an urgent need for supplementary immunization activities targeting susceptible health care workers, unvaccinated or incompletely vaccinated adults as well as people without vaccination records. The comprehensive investigation of the 2014/2015 measles resurgence will contribute to decisions about appropriate countermeasures to stop the future measles resurgences in Serbia.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0224009PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6797132PMC
March 2020

Cross-species transmission of poultry pathogens in backyard farms: ducks as carriers of chicken viruses.

Avian Pathol 2019 Dec 24;48(6):503-511. Epub 2019 Jul 24.

Department of Infection and Immunity, Luxembourg Institute of Health , Esch-sur-Alzette , Luxembourg.

In backyard farms of Lao People's Democratic Republic, mixed-species rearing of poultry is a breeding-ground for cross-species transmission. Here, the epidemiology of viruses circulating among backyard poultry in Vientiane Province was assessed to guide future control strategies. Oral/tracheal and cloacal swabs, collected from 605 poultry (308 ducks, 297 chickens) between 2011 and 2015, were screened by PCR for Newcastle disease virus (NDV), coronavirus (CoV) and chicken anaemia virus (CAV). Chicken sera were screened for anti-NDV antibodies by ELISA. Statistical and phylogenetic analyses revealed transmission patterns and relationships. Closely related strains co-circulated in chickens and ducks. While CoV RNA was detected in oral/tracheal swabs of 9.3% of the chickens and 2.4% of the ducks, rates were higher in faecal swabs of both species (27.3% and 48.2%). RNA of infectious bronchitis virus (IBV) and duck CoV was found in faecal swabs of chickens (19.7% and 7.1%) and ducks (4.1% and 44.1%). Moreover, DNA of the generally chicken-specific CAV was detected in oral/tracheal swabs of chickens (18.1%) and, sporadically, of ducks (2.4%). Despite serological evidence of NDV circulation or vaccination (86.9%), NDV RNA was not detected. We found a high prevalence and indication for cross-species transmission of different CoV strains in backyard poultry. Interestingly, ducks served as biological, or at least mechanical, carriers of viral strains closely related not only to IBV, but also to CAV. Bird containment and poultry species separation could be first steps to avoid cross-species transmission and emergence of novel strains with broad host range and enhanced pathogenicity. High rates of avian viruses were detected by PCR in backyard poultry from Lao PDR. Diverse coronavirus and chicken anemia virus strains co-circulated. Phylogenetic analyses suggested virus transmission between chickens and ducks. Serological evidence of Newcastle disease was found, but viral RNA was not detected.
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http://dx.doi.org/10.1080/03079457.2019.1628919DOI Listing
December 2019

Varicella zoster and fever rash surveillance in Lao People's Democratic Republic.

BMC Infect Dis 2019 May 8;19(1):392. Epub 2019 May 8.

Institut Pasteur du Laos, Vientiane, Lao People's Democratic Republic.

Background: In Lao PDR, the epidemiology of varicella infection is uncertain, since it is not a notifiable disease and VZV outbreaks are rarely reported as fever/rash (F/R) diseases.

Methods: We estimated the seroprevalence of VZV (IgG ELISA) in different age cohorts (9 months to 46 years; N = 3139) and investigated VZV and 6 other viruses in patients during F/R outbreaks and in an ad hoc sentinel site in the context of the national reporting system (IgM ELISA, PCR).

Results: At least 80% of the sampled population had evidence of VZV infection before the age of 15. The largest increase in seroprevalence occurred between the age groups 1 to 5 and 6 to 7 year-olds. A VZV outbreak (clade 2) also occurred in this age group mostly during the first year of primary school (median age 6 years, interquartile range 4.0-7.5). During a dengue outbreak, 6% had varicella. At our F/R sentinel site, 14% of children with viral etiology were laboratory diagnosed as varicella and among others, a sizeable number of measles (N = 12) and rubella cases (N = 25) was detected compared to those reported for the whole country (N = 56 and 45), highlighting nationwide a large challenge of underreporting or misdiagnosis of these notifiable diseases because of lack of diagnostic laboratory capacity.

Conclusion: We recommend strengthening the clinical and laboratory diagnosis of VZV, measles and rubella, the surveillance and reporting of notifiable F/R diseases by retraining of healthcare workers and by setting up sentinel sites and enhancing laboratory capacity.
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http://dx.doi.org/10.1186/s12879-019-3990-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6507166PMC
May 2019

Identification of human parvovirus B19 among measles and rubella suspected patients from Cuba.

J Med Virol 2019 07 14;91(7):1351-1354. Epub 2019 Mar 14.

Department of Infection and Immunity, Infectious Diseases Research Unit, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg.

Between September 2014 and December 2015, 298 sera from rash and fever patients from all over Cuba were investigated for specific IgM antibodies against measles, rubella, dengue, human parvovirus B19 (B19V) and human herpesvirus 6 (HHV6) using a commercial enzyme-linked immunosorbent assay kits. B19V IgM positive and equivocal samples were investigated by a polymerase chain reaction and genotyping. No measles, rubella or dengue cases were detected. HHV6-IgM antibodies were confirmed in 5.7% and B19V-IgM antibodies in 10.7% of the patients. A total of 31.3% of the B19V cases were between 5 and 9 years old and 34.4% were 20 years and older. The only B19V sequence obtained belonged to genotype 1a. Diagnosis was established for only 16% of the rash and fever patients, suggesting that other diseases such as Zika or Chikungunya may play a role.
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http://dx.doi.org/10.1002/jmv.25444DOI Listing
July 2019

High circulation of Hepatitis E virus in pigs and professionals exposed to pigs in Laos.

Zoonoses Public Health 2018 12 27;65(8):1020-1026. Epub 2018 Aug 27.

Lao-Lux-Laboratory, Institute Pasteur du Laos, Vientiane, Lao People's Democratic Republic.

Epidemiological characteristics of hepatitis E Virus (HEV) differ due to the vast spatial heterogeneity in sanitation status, dietary habits and extent of exposure to animals. Although HEV infections are mostly asymptomatic, prognosis is poor for patients with compromised immune systems or pre-existing liver disease and during pregnancy. In developing countries, low hygienic standards and close human-animal interactions at farms and slaughterhouses likely favour zoonotic transmission of the virus. In this cross-sectional study from Lao People's Democratic Republic, anti-HEV IgG was detected by ELISA in 54.0% (136/252) of slaughter pigs, in 41.0% (57/139) of professionals exposed to pigs and in 18.1% of the nonrisk controls (38/210). We show that people occupationally exposed to pigs are at higher risk of infection (p < 0.001). In particular, contact to young piglets as compared to contact to the older slaughter pigs was a major risk factor (p = 0.011). Besides, consumption of bottled water significantly reduced the risk of infection (p = 0.018). In conclusion, we show that in Lao PDR, the high endemicity of HEV, the inadequate implementation of hygiene measures and the limited access to safe water jeopardize the health of professionals exposed to pigs.
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http://dx.doi.org/10.1111/zph.12520DOI Listing
December 2018

Mumps epidemiology in Cuba between 2004 and 2015.

Arch Virol 2018 Nov 4;163(11):3059-3064. Epub 2018 Aug 4.

Infectious Diseases Research Unit, Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg.

Vaccination with the measles, mumps and rubella vaccine decreased the mumps incidence in Cuba, but in 2006 and 2007 an outbreak with more than 1000 laboratory confirmed cases occurred, mainly among high school and university students. The objective of the study was to investigate mumps epidemiology in Cuba between 2004 and 2015 and provide an in-depth laboratory characterization of selected samples from mumps patients. Samples from 116 cases (throat swabs, urines, paired acute and convalescent serum samples) were tested for mumps-specific IgM antibodies by ELISA, in a hemagglutination inhibition assay (HIA) or by RT-PCR. IgM antibodies were found in 80.2% of cases. 48.3% of first sera were positive, 30 of which were collected within two days after symptom onset. Testing of all 116 paired sera by HIA showed seroconversion in 55.2% individuals and an at least fourfold increase in antibodies in 44.8% of cases. In 18 out of the 111 vaccinated people (16.2%) no IgM antibodies were detected, neither in the acute nor the convalescent sera, but 14 of them showed seroconversion by HIA and 4 had an at least fourfold increase of hemagglutinin antibody titers. In the RT-PCR, 23 acute phase sera, 4 throat swabs and 5 urines were positive. Detection of mumps-specific IgM antibodies by ELISA and additional diagnostic methods may be required in settings with high vaccination coverage rates.
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http://dx.doi.org/10.1007/s00705-018-3946-zDOI Listing
November 2018

Measles virus genotype D4 strains with non-standard length M-F non-coding region circulated during the major outbreaks of 2011-2012 in Spain.

PLoS One 2018 16;13(7):e0199975. Epub 2018 Jul 16.

National Reference Laboratory for Measles and Rubella, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.

In recent decades, vaccination has substantially reduced the number of measles cases to levels close to the elimination stage. However, major measles outbreaks occurred in Europe during 2010-2012, after the introduction of the D4-Enfield lineage. We have performed a molecular characterization of 75 measles virus genotype D4 strains from patients infected in Spain between 2004 and 2012 by sequencing the N-450 region and the M-F non-coding region (M-F NCR) in order to identify genetic features of these viruses. The analysis of the N-450 region confirmed that all samples obtained since 2008 belonged to variants or sets of identical sequences of the D4-Enfield lineage, including a new one named MVs/Madrid.ESP/46.10/. Analysis of the M-F NCR showed insertions and deletions associated with previously described, uncommon non-standard genome length measles viruses. This genetic feature was identified in the D4-Enfield lineage viruses, but not in the other D4 viruses that were circulating in Spain before 2008, suggesting that these non-standard length M-F NCR sequences are characteristic of the D4-Enfield lineage. The results of the phylogenetic analysis of Spanish M-F NCRs suggest higher resolution in discriminating strains than did the N-450 analysis. In addition, the results of the analysis of the M-F NCR on the MVs/Madrid.ESP/46.10/ sub-lineage seem to support the potential utility of this region as a tool for epidemiological surveillance complementary to the N-450 region, as previously suggested. Further investigation on this question, as well as the surveillance of new potentially emerging strains with non-standard length M-F NCR are strongly recommended as part of future strategies for measles elimination.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0199975PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6047782PMC
January 2019

Rubella Viruses Shift Cellular Bioenergetics to a More Oxidative and Glycolytic Phenotype with a Strain-Specific Requirement for Glutamine.

J Virol 2018 09 16;92(17). Epub 2018 Aug 16.

Institute of Virology, University of Leipzig, Leipzig, Germany

The flexible regulation of cellular metabolic pathways enables cellular adaptation to changes in energy demand under conditions of stress such as posed by a virus infection. To analyze such an impact on cellular metabolism, rubella virus (RV) was used in this study. RV replication under selected substrate supplementation with glucose, pyruvate, and glutamine as essential nutrients for mammalian cells revealed its requirement for glutamine. The assessment of the mitochondrial respiratory (based on the oxygen consumption rate) and glycolytic (based on the extracellular acidification rate) rate and capacity by respective stress tests through Seahorse technology enabled determination of the bioenergetic phenotype of RV-infected cells. Irrespective of the cellular metabolic background, RV infection induced a shift of the bioenergetic state of epithelial cells (Vero and A549) and human umbilical vein endothelial cells to a higher oxidative and glycolytic level. Interestingly there was a RV strain-specific, but genotype-independent demand for glutamine to induce a significant increase in metabolic activity. While glutaminolysis appeared to be rather negligible for RV replication, glutamine could serve as donor of its amide nitrogen in biosynthesis pathways for important metabolites. This study suggests that the capacity of RVs to induce metabolic alterations could evolve differently during natural infection. Thus, changes in cellular bioenergetics represent an important component of virus-host interactions and could complement our understanding of the viral preference for a distinct host cell population. RV pathologies, especially during embryonal development, could be connected with its impact on mitochondrial metabolism. With bioenergetic phenotyping we pursued a rather novel approach in virology. For the first time it was shown that a virus infection could shift the bioenergetics of its infected host cell to a higher energetic state. Notably, the capacity to induce such alterations varied among different RV isolates. Thus, our data add viral adaptation of cellular metabolic activity to its specific needs as a novel aspect to virus-host evolution. In addition, this study emphasizes the implementation of different viral strains in the study of virus-host interactions and the use of bioenergetic phenotyping of infected cells as a biomarker for virus-induced pathological alterations.
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http://dx.doi.org/10.1128/JVI.00934-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6096829PMC
September 2018

Influenza D Virus Circulation in Cattle and Swine, Luxembourg, 2012-2016.

Emerg Infect Dis 2018 07;24(7):1388-1389

We detected antibodies against influenza D in 80.2% of the cattle sampled in Luxembourg in 2016, suggesting widespread virus circulation throughout the country. In swine, seroprevalence of influenza D was low but increased from 0% to 5.9% from 2012 to 2014-2015.
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http://dx.doi.org/10.3201/eid2407.171937DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6038750PMC
July 2018

Evidence of increased Hepatitis E virus exposure in Lao villagers with contact to ruminants.

Zoonoses Public Health 2018 09 10;65(6):690-701. Epub 2018 Jun 10.

Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Grand-Duchy of Luxembourg.

Although pigs are the main reservoir, ruminants have also been shown to be susceptible to hepatitis E virus (HEV). We investigated zoonotic transmission of HEV in rural settings of Lao People's Democratic Republic (Lao PDR) where humans are in close contacts with ruminants and where pigs are rare. Villagers with (n = 171, risk group) and without (n = 155, control group) cattle were recruited in seven villages in Vientiane Capital. Owners of pigs were excluded. Blood, as well as information on socio-demographics, animal contact, dietary habits and awareness of zoonoses were collected to assess risk factors. Blood and rectal swabs were collected from cattle (n = 173) and other ruminants (27 goat, 5 buffaloes) to measure anti-HEV antibody and virus prevalence. A similar anti-HEV antibody seroprevalence was found in cattle (6.8%) and other ruminants (8%). HEV RNA was detected in none of the animal rectal swabs and human sera. Anti-HEV IgG seroprevalence was higher in cattle farmers than in the control group (59.1% vs. 43.9%, p = 0.008) and increased significantly with age. Other risk factors included male gender, close contact with cattle and consumption of undercooked meat. We find that HEV is highly endemic in rural Laos and provide first evidence that HEV circulates in free-roaming ruminants with open access to village water sources. Despite some awareness about hygiene, villagers are likely constantly exposed to zoonotic diseases by dietary and lifestyle habits. Cattle farmers had a higher risk of HEV infection than other villagers. Our study highlights the need to raise the awareness of the rural population about water- and food-borne pathogens, and about the role of cattle as a possible source of infection. The knowledge gained on local risk factors and husbandry conditions should guide future awareness raising campaigns and promote appropriate hygienic measures including handwashing and the consumption of safe food and water.
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http://dx.doi.org/10.1111/zph.12483DOI Listing
September 2018

Immunity levels to poliovirus in Lao children and adults before the vaccine-derived poliovirus outbreak: A retrospective study.

PLoS One 2018 15;13(5):e0197370. Epub 2018 May 15.

Infectious Diseases Research Unit, Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg.

In 2015, several provinces in Lao People's Democratic Republic (Lao PDR) experienced a vaccine-derived poliovirus outbreak. This survey was conducted (i) to evaluate the vaccination coverage in different settings and cohorts using the seroprevalence of anti-poliovirus (PV) antibodies as a surrogate measure, and (ii) to explore the usefulness of an ELISA in a country with limited resources and a specific epidemiological setting. IgG antibodies were assessed by ELISA in Lao children (n = 1216) and adults (n = 1228), including blood donors and health care workers. Protective antibody titers against the 3 vaccine serotypes were determined by microneutralization (VNT) in a subset of participants. More than 92% of the children had anti-poliovirus antibodies, regardless of nutritional status or access to health care, highlighting the success of the vaccination outreach activities in the country. In contrast, anti-poliovirus seroprevalence reached only 81.7% in blood donors and 71.9% in health care workers. Participants born before the introduction of poliovirus vaccination in Lao PDR were considerably less likely to be seropositive. These findings align with the epidemiology of the outbreak. Neutralizing antibodies against at least one of the 3 poliovirus serotypes were detected in all children (99/99) and 93/99 had antibodies against all serotypes. Similarly, all health care workers had neutralizing antibodies against at least one and 92/99 against all serotypes. The comparison of both assays shows an acceptable underestimation of vaccine coverage in children by ELISA, but a low sensitivity of the ELISA in the adults. We show that the ELISA is a reasonable alternative to the VNT in particular in vaccinated children, that an improved version should be serotype specific, and that negativity thresholds should be revisited for optimal sensitivity and specificity. Thus, polio-free countries with an uncertain vaccination coverage and limited laboratory capacity, that are at risk of vaccine-derived poliovirus outbreaks or of re-importation of wild poliovirus may benefit from an improved ELISA for cohort studies to evaluate their immunization program in children.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0197370PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5953481PMC
November 2018

Prevalence of Hepatitis B virus and Hepatitis D virus Coinfection in Western Burkina Faso and molecular characterization of the detected virus strains.

Int J Infect Dis 2018 May 9;70:15-19. Epub 2018 Feb 9.

Infectious Diseases Research Unit, Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg. Electronic address:

Objectives: In this study, we monitored the seroprevalence of HBV-HDV co-infection in different population groups in the Western part of Burkina Faso, and described the genetic diversity of the detected virus strains.

Methods: Between October 2013 and December 2014, venous blood samples were collected from different cohorts (blood donors, pregnant women, outpatients) in the western region of Burkina Faso. Samples were tested for HBsAg and total anti-HDV antibodies. Positive samples were further analysed for HBV-DNA and HDV-RNA. Genotyping of the detected virus strains was done by nucleotide sequencing and phylogenetic analyses.

Results: A total of 841 participants were included in this study. The mean age was 27.45 years (range: 7-89 years). HBsAg was found in 117 (13.9%) participants. Of the HBsAg positive samples, 4 (3.4%) were positive for total anti-HDV antibodies and negative for HDV RNA. Phylogenetic analyses based on the HBV complete genome (n=10) and S fragment sequences (n=35) showed that all strains belonged to genotype E.

Conclusions: Our study showed a high HBsAg prevalence, but a low rate of HDV co-infection in HBsAg carriers from western Burkina Faso. The predominance of HBV genotype E in the country was confirmed. Our findings contribute to a better understanding of the burden of HBV and HDV infection in western Burkina Faso.
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http://dx.doi.org/10.1016/j.ijid.2018.02.004DOI Listing
May 2018

Epidemiology and molecular characterization of influenza viruses in Burkina Faso, sub-Saharan Africa.

Influenza Other Respir Viruses 2018 07 24;12(4):490-496. Epub 2018 Apr 24.

Infectious Diseases Research Unit, Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg.

Background: The importance of influenza viruses in respiratory infections in sub-Saharan Africa has been historically overlooked, including in Burkina Faso.

Objectives: This study therefore aimed at evaluating the prevalence and seasonal occurrence of influenza viruses in children under 5 years old, at risk of influenza-related complications, presenting with influenza-like illness (ILI) or severe acute respiratory infection (SARI). The study also aimed at identifying the periods with increased influenza transmission for vaccination recommendations in Burkina Faso.

Methods: From January 2014 to December 2015, ILI and SARI (2015 only) patients were recruited in six healthcare centers in Burkina Faso. Influenza A and B molecular detection and subtyping were performed. Clade clustering of a subset of A(H1N1)pdm09 and A(H3N2) strains was deduced by performing phylogenetic analyses on hemagglutinin gene sequences. Weekly surveillance data from FluNet (2011-2013; 2016) and this study (2014-2015) were used to identify periods of increased influenza activity.

Results: Influenza A and B viruses were detected in 15.1% (112 of 743) of ILI and 6.6% (12 of 181) of SARI patients. Overall, influenza A viruses were largely predominant (81 of 124, 65.3%), with 69.1% of A(H3N2) and 30.9% of A(H1N1)pdm09 strains. Four waves of increased transmission were identified in 2014-2015, each dominated by different influenza subtypes and clades. Between 2011 and 2016, periods of increased influenza activity varied in their frequency, duration, and timing.

Conclusion: Influenza A and B viruses were detected in a substantial number of ILI and SARI cases in Burkina Faso. Vaccination in September-October would likely protect the highest number of patients.
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http://dx.doi.org/10.1111/irv.12539DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6005621PMC
July 2018

IgG antibody prevalence suggests high immunization needs in newcomers to Luxembourg, 2012.

Vaccine 2018 02 3;36(6):899-905. Epub 2018 Jan 3.

WHO European Regional Reference Laboratory for Measles and Rubella, Department of Infection and Immunity, Luxembourg Institute of Health, 29 rue Henri Koch, L-4354 Esch-sur-Alzette and Laboratoire National de Santé, 1 rue Louis Rech, L-3555 Dudelange, Luxembourg. Electronic address:

Vaccine coverage of the general population in Luxembourg is high, but refugees or asylum seekers may be incompletely vaccinated and susceptible to vaccine-preventable diseases. In order to assess protection rates, serum and oral fluid samples were collected from 406 newcomers aged between 13 and 70 years arriving between May and September 2012. Sera were screened for IgG antibodies against measles, rubella, mumps, hepatitis B, tetanus, diphtheria and pertussis. Oral fluid samples were screened for antibodies against measles, mumps and rubella virus to investigate their suitability for antibody prevalence studies. More than 90% of the participants had IgG antibodies against rubella, 73% against measles and 56% against mumps. Less than 19% had anti-HBs antibodies. Nearly 84% of the participants had an adequate protection against tetanus, 73% against diphtheria and 40% had pertussis antibodies. 93%, 95% and 78% of the measles, rubella and mumps test results obtained with serum and oral fluid were concordant. The majority of the participants lacked antibodies against at least one of the measles/mumps/rubella (58%) and diphtheria/tetanus/pertussis (72%) vaccine components and against hepatitis B virus (82%) and might thus profit from vaccination. Oral fluid is a suitable alternative and non-invasive specimen for measles/rubella antibody prevalence studies.
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http://dx.doi.org/10.1016/j.vaccine.2017.12.041DOI Listing
February 2018

Hepatitis B, C and D virus genotypes detected in HBsAg- or anti-HCV-positive people from the Republic of Moldova.

Arch Virol 2018 Feb 8;163(2):431-438. Epub 2017 Nov 8.

Infectious Diseases Research Unit, Department of Infection and Immunity, Luxembourg Institute of Health, 29, rue Henri Koch, 4354, Esch-sur-Alzette, Luxembourg.

In the Republic of Moldova, little is known about hepatitis B, C and D virus (HBV, HCV, HDV) genotypes, although the genetic variant may influence the course and outcome of disease. For HBV genotyping, 301 hepatitis B surface antigen (HBsAg)-positive sera collected in 2010 and 2011 from drug users, prison inmates, commercial sex workers, and the general population in different geographical regions were investigated. The 31 HBsAg-positive sera collected in 2011 were also tested for HDV. Eighty-eight anti-HCV-positive sera collected between 2010 and 2011 from the general population and health care workers were used for HCV genotyping. Phylogenetic analysis of 84 HBV sequences showed that most of the viruses belonged to genotype D (n = 82, 97.6%), predominantly to the subgenotype D1/D2 cluster (n = 75/82, 91.5%). One sequence (74110) clustered as an outlier to this cluster, and six sequences belonged to subgenotype D3. Only two subgenotype A2 sequences were found. Cloning of six samples with ambiguous sequence chromatogram signals showed no mixed infections. Phylogenetic analysis of HCV sequences from 66 patients showed a predominance of subtype 1b (n = 63, 95.5%). Two sequences belonged to subtype 3a, and one to subtype 2a. HDV RNA belonging to genotype 1 was found in two sera (2/31, 6.5%). Thus, genotypes prevalent in Europe were detected for all three hepatitis viruses. For both HBV and HCV, one genotype was dominant, while occasional other variants seem to be restricted to certain cohorts and/or transmission routes.
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http://dx.doi.org/10.1007/s00705-017-3632-6DOI Listing
February 2018

Transcription-associated mutational pressure in the Parvovirus B19 genome: Reactivated genomes contribute to the variability of viral populations.

J Theor Biol 2017 12 21;435:199-207. Epub 2017 Sep 21.

Laboratory of Cellular Technologies, Institute of Phisiology of the National Academy of Sciences of Belarus, Academicheskaya, 28, Minsk, Belarus.

In this study we used non-overlapping parts of the two long open reading frames coding for nonstructural (NS) and capsid (VP) proteins of all available sequences of the Parvovirus B19 subgenotype 1a genome and found out that the rates of A to G, C to T and A to T mutations are higher in the first long reading frame (NS) of the virus than in the second one (VP). This difference in mutational pressure directions for two parts of the same viral genome can be explained by the fact of transcription of just the first long reading frame during the lifelong latency in nonerythroid cells. Adenine deamination (producing A to G and A to T mutations) and cytosine deamination (producing C to T mutations) occur more frequently in transcriptional bubbles formed by DNA "plus" strand of the first open reading frame. These mutations can be inherited only in case of reactivation of the infectious virus due to the help of Adenovirus that allows latent Parvovirus B19 to start transcription of the second reading frame and then to replicate its genome by the rolling circle mechanism using the specific origin. Results of this study provide evidence that the genomes reactivated from latency make significant contributions to the variability of Parvovirus B19.
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http://dx.doi.org/10.1016/j.jtbi.2017.09.019DOI Listing
December 2017

Ongoing mumps outbreak in Israel, January to August 2017.

Euro Surveill 2017 Aug;22(35)

Division of Epidemiology, Ministry of Health, Jerusalem, Israel.

In Israel, 262 mumps cases were registered between 1 January and 28 August 2017 despite a vaccine coverage of ≥ 96%. The majority (56.5%) of cases were adolescents and young adults between 10 and 24 years of age. Nearly twice as many cases were reported in males than in females. Sequence information identified genotype G and suggested specific transmission chains in different religious communities, with the Muslim population in Jerusalem being most severely affected.
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http://dx.doi.org/10.2807/1560-7917.ES.2017.22.35.30605DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5587898PMC
August 2017

Novel Alphacoronaviruses and Paramyxoviruses Cocirculate with Type 1 and Severe Acute Respiratory System (SARS)-Related Betacoronaviruses in Synanthropic Bats of Luxembourg.

Appl Environ Microbiol 2017 09 31;83(18). Epub 2017 Aug 31.

Infectious Diseases Research Unit, Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg.

Several infectious disease outbreaks with high mortality in humans have been attributed to viruses that are thought to have evolved from bat viruses. In this study from Luxembourg, the genetic diversity and epidemiology of paramyxoviruses and coronaviruses shed by the bat species and were evaluated. Feces collection ( = 624) was performed longitudinally in a mixed-species colony in 2015 and 2016. In addition, feces ( = 254) were collected cross-sectionally from six colonies in 2016. By use of degenerate primers in a nested format, overall prevalences of 1.1% (10/878) and 4.9% (43/878) were determined for paramyxoviruses and coronaviruses. Sequences of the partial RNA-dependent RNA polymerase and spike glycoprotein genes of coronaviruses, as well as sequences of the partial L gene of paramyxoviruses, were obtained. Novel paramyxovirus and strains were identified in different colonies, and severe acute respiratory syndrome (SARS)-related strains were shed by Logistic regression revealed that the level of shedding was highest in July (odds ratio, 2.8; < 0.01), probably due to periparturient stress. Phylogenetic analyses point to close virus-host coevolution, and the high genetic similarity of the study strains suggests that the colonies in Luxembourg are socially connected. Most interestingly, we show that bats also host strains. The high similarity of the spike gene sequences of these viruses with mammalian strains may be of concern. Both the SARS-related and strains detected in bats in Luxembourg may cross the species barrier after a host adaptation process. Bats are a natural reservoir of a number of zoonotic pathogens. Several severe outbreaks in humans (e.g., a Nipah virus outbreak in Malaysia in 1998, and the almost global spread of severe acute respiratory syndrome in 2003) have been caused by bat-borne viruses that were transmitted to humans mostly after virus adaptation (e.g., in intermediate animal hosts). Despite the indigenousness of bat species that host viruses with suspected zoonotic potential and despite the zoonotic transmission of European bat 1 lyssavirus in Luxembourg, knowledge about the diversity and epidemiology of bat viruses remains limited in this country. Moreover, in contrast to other European countries, bat viruses are currently not included in the national surveillance activities of this land-locked country. We suggest that this gap in disease surveillance should be addressed, since we show here that synanthropic bats host viruses that may be able to cross the species barrier.
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http://dx.doi.org/10.1128/AEM.01326-17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5583486PMC
September 2017

Molecular epidemiology of Avian Rotaviruses Group A and D shed by different bird species in Nigeria.

Virol J 2017 06 12;14(1):111. Epub 2017 Jun 12.

Infectious Diseases Research Unit, Department of Infection and Immunity, Luxembourg Institute of Health, 29 rue Henri Koch, L-4354, Esch-sur-Alzette, Luxembourg.

Background: Avian rotaviruses (RVs) cause gastrointestinal diseases of birds worldwide. However, prevalence, diversity, epidemiology and phylogeny of RVs remain largely under-investigated in Africa.

Methods: Fecal samples from 349 birds (158 symptomatic, 107 asymptomatic and 84 birds without recorded health status) were screened by reverse transcription PCR to detect RV groups A and D (RVA and RVD). Partial gene sequences of VP4, VP6, VP7 and NSP4 for RVA, and of VP6 and VP7 for RVD were obtained and analyzed to infer phylogenetic relationship. Fisher's exact test and logistic regression were applied to identify factors potentially influencing virus shedding in chickens.

Results: A high prevalence of RVA (36.1%; 126/349) and RVD (31.8%; 111/349) shedding was revealed in birds. In chickens, RV shedding was age-dependent and highest RVD shedding rates were found in commercial farms. No negative health effect could be shown, and RVA and RVD shedding was significantly more likely in asymptomatic chickens: RVA/RVD were detected in 51.9/48.1% of the asymptomatic chickens, compared to 18.9/29.7% of the symptomatic chickens (p < 0.001/p = 0.01). First RVA sequences were obtained from mallard ducks (Anas platyrhynchos) and guinea fowls (Numida meleagris). Phylogenetic analyses illustrated the high genetic diversity of RVA and RVD in Nigerian birds and suggested cross-species transmission of RVA, especially at live bird markets. Indeed, RVA strains highly similar to a recently published fox rotavirus (RVA/Fox-tc/ITA/288356/2011/G18P[17]) and distantly related to other avian RVs were detected in different bird species, including pigeons, ducks, guinea fowls, quails and chickens.

Conclusion: This study provides new insights into epidemiology, diversity and classification of avian RVA and RVD in Nigeria. We show that cross-species transmission of host permissive RV strains occurs when different bird species are mixed.
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http://dx.doi.org/10.1186/s12985-017-0778-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5469043PMC
June 2017

Hepatitis B virus infection assessed 3 to 18 years after vaccination in Cuban children and adolescents born to HBsAg-positive mothers.

Arch Virol 2017 Aug 24;162(8):2393-2396. Epub 2017 Apr 24.

Infectious Diseases Research Unit, Department of Infection and Immunity, Luxembourg Institute of Health, 29, rue Henri Koch, L-4354, Esch-Sur-Alzette, Grand Duchy of Luxembourg.

Thirty-two participants, aged between 3-18 years, born to hepatitis B surface antigen (HBsAg)-positive mothers and vaccinated at birth were analyzed for hepatitis B virus (HBV) infection. Overall, 56% had anti-HB titers ≥10 IU/L; five were positive for antibodies to the core antigen (anti-HBc), and two of these were also positive for HBsAg/DNA. One of the HBsAg/anti-HBc double-negative children presented with an unusual occult infection (HBV DNA-positive). No known vaccine escape mutations were detectable. Our data suggest that the vaccine protected 93.8% of children in this high-risk group against chronic HBV infection. Occult infections should be considered even in countries with low endemicity and high vaccination coverage.
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http://dx.doi.org/10.1007/s00705-017-3365-6DOI Listing
August 2017

Epidemiological and molecular investigation of a rubella outbreak, Romania, 2011 to 2012.

Euro Surveill 2016 Sep;21(38)

National Institute of Research-Development for Microbiology and Immunology "Cantacuzino", Bucharest, Romania.

We describe a rubella outbreak that occurred in Romania between September 2011 and December 2012. During this period 24,627 rubella cases, 41.1% (n=10,134) of which female, were notified based on clinical criteria, and a total of 6,182 individuals were found serologically positive for IgM-specific rubella antibody. The median age of notified cases was 18 years (range: <1-65) and the most affected age group 15 to 19 years (n=16,245 cases). Of all notified cases, 24,067 cases (97.7%) reported no history of vaccination. Phylogenetic analysis of 19 sequences (739 nucleotides each), from 10 districts of the country revealed that the outbreak was caused by two distinct rubella virus strains of genotype 2B, which co-circulated with both temporal and geographical overlap. In addition to the 6,182 IgM-positive rubella cases, 28 cases of congenital rubella syndrome (CRS) were identified, including 11 neonatal deaths and one stillbirth. The outbreak underscores the need to encourage higher vaccination uptake in the population, particularly in women of reproductive age, and to strengthen epidemiological and laboratory investigations of suspected rubella cases. Genetic characterisation of wild-type rubella virus is an essential component to enhance surveillance and here we report rubella virus sequences from Romania.
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http://dx.doi.org/10.2807/1560-7917.ES.2016.21.38.30345DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5073198PMC
September 2016