Pan- #Filovirus #Serum Neutralizing #Antibodies in a Subset of #Congolese #Ebolavirus Infection #Survivors (J Infect Dis., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Pan-Filovirus Serum Neutralizing Antibodies in a Subset of Congolese Ebolavirus Infection Survivors.

Bramble MS1,2, Hoff N1, Gilchuk P3, Mukadi P4, Lu K5, Doshi RH1, Steffen I5, Nicholson BP6, Lipson A1, Vashist N2, Sinai C1, Spencer D1, Olinger G7, Wemakoy EO8, Illunga BK9, Pettitt J10, Logue J10, Marchand J10, Varughese J10, Bennett RS10, Jahrling P10, Cavet G11, Serafini T11, Ollmann Saphire E12,13, Vilain E2, Muyembe-Tamfum JJ4, Hensely LE10,14, Simmons G5, Crowe JE Jr3,15, Rimoin AW1.

Author information: 1 Department of Epidemiology, School of Public Health, University of California, Los Angeles. 2 Department of Genetic Medicine Research, Children’s Research Institute, Children’s National Medical Center, Washington, District of Columbia. 3 Vanderbilt Vaccine Center, and Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee. 4 Institut National de Recherche Biomedicale, Kinshasa, Democratic Republic of the Congo. 5 Blood Systems Research Institute, and Department of Laboratory Medicine, University of California, San Francisco. 6 Institute for Medical Research, Durham Veterans Affairs Medical Center, North Carolina. 7 Boston University, School of Medicine, Department of Medicine, Massachusetts. 8 Kinshasa School of Public Health, Kinshasa, Democratic Republic of the Congo. 9 Direction de la Lutte Contre les Maladies, Ministère de la Sante, Kinshasa, Democratic Republic of the Congo. 10 Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Frederick, Maryland. 11 Atreca, Inc, Redwood City. 12 Skaggs Institute for Chemical Biology, La Jolla, California. 13 Department of Immunology and Microbial Science, Scripps Research Institute, La Jolla, California. 14 Emerging Viral Pathogens Section, NIAID, NIH, Frederick, Maryland. 15 Departments of Pediatrics and Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee.



One year after a Zaire ebolavirus (EBOV) outbreak occurred in the Boende Health Zone of the Democratic Republic of the Congo during 2014, we sought to determine the breadth of immune response against diverse filoviruses including EBOV, Bundibugyo (BDBV), Sudan (SUDV), and Marburg (MARV) viruses. After assessing the 15 survivors, 5 individuals demonstrated some degree of reactivity to multiple ebolavirus species and, in some instances, Marburg virus. All 5 of these survivors had immunoreactivity to EBOV glycoprotein (GP) and EBOV VP40, and 4 had reactivity to EBOV nucleoprotein (NP). Three of these survivors showed serologic responses to the 3 species of ebolavirus GPs tested (EBOV, BDBV, SUDV). All 5 samples also exhibited ability to neutralize EBOV using live virus, in a plaque reduction neutralization test. Remarkably, 3 of these EBOV survivors had plasma antibody responses to MARV GP. In pseudovirus neutralization assays, serum antibodies from a subset of these survivors also neutralized EBOV, BDBV, SUDV, and Taï Forest virus as well as MARV. Collectively, these findings suggest that some survivors of naturally acquired ebolavirus infection mount not only a pan-ebolavirus response, but also in less frequent cases, a pan-filovirus neutralizing response.

PMID: 30107445 PMCID: PMC6217721 DOI: 10.1093/infdis/jiy453 [Indexed for MEDLINE]  Free PMC Article

Keywords: Ebola; Filovirus; Marburg; Serology.



High #correlation between #Zika virus NS1 #antibodies and neutralizing antibodies in selected #serum samples from normal healthy #Thais (Sci Rep., abstract)

[Source:  Scientific Reports, full page: (LINK). Abstract, edited.]

High correlation between Zika virus NS1 antibodies and neutralizing antibodies in selected serum samples from normal healthy Thais

Wannapa Sornjai, Suwipa Ramphan, Nitwara Wikan, Prasert Auewarakul & Duncan R. Smith

Scientific Reports, volume 9, Article number: 13498 (2019)



Despite the widespread presence of the mosquito transmitted Zika virus (ZIKV) over much of Southeast Asia, the number of reported cases remains low. One possibility is that residents in Southeast Asia are immunologically protected, although the nature of any such protection remains unclear. This study sought to investigate the presence of antibodies directed to ZIKV NS1 protein in a selected sub-set of samples from a well characterized cohort of serum samples from normal, healthy Thais that had been previously characterized for the presence of neutralizing antibodies to ZIKV, DENV 1-4, and JEV. Because of similarities in molecular weight between the flavivirus E and NS1 proteins, an immunoblot system was established in which the NS1 antigen was not denatured, allowing detection of the dimer form of NS1, distinctly clear from the migration position of the E and NS1 monomer proteins. The results showed that antibodies to ZIKV NS1 protein were only detected in samples with ZIKV neutralizing antibodies (27/30 samples), and no sample (0/30) with a ZIKV plaque reduction neutralization test (PRNT)90 < 20 showed evidence of anti-ZIKV NS1 antibodies. The high correlation between the presence of ZIKV NS1 antibodies and ZIKV PRNT suggests that immunological protection against ZIKV infection in Thailand arises from prior exposure to ZIKV, and not through cross neutralization.

Keywords: Zika Virus; Serology; Thailand.


#Dengue and #chikungunya among outpatients with acute undifferentiated #fever in #Kinshasa, #DRC: A cross-sectional study (PLoS Negl Trop Dis., abstract)

[Source: PLoS Neglected Tropical Diseases, full page: (LINK). Abstract, edited.]


Dengue and chikungunya among outpatients with acute undifferentiated fever in Kinshasa, Democratic Republic of Congo: A cross-sectional study

Sam Proesmans , Freddy Katshongo, John Milambu, Blaise Fungula, Hypolite Muhindo Mavoko, Steve Ahuka-Mundeke, Raquel Inocêncio da Luz, Marjan Van Esbroeck, Kevin K. Ariën, Lieselotte Cnops, Birgit De Smet, Pascal Lutumba, Jean-Pierre Van geertruyden, Veerle Vanlerberghe

Published: September 5, 2019 / DOI: / This is an uncorrected proof.




Pathogens causing acute fever, with the exception of malaria, remain largely unidentified in sub-Saharan Africa, given the local unavailability of diagnostic tests and the broad differential diagnosis.


We conducted a cross-sectional study including outpatient acute undifferentiated fever in both children and adults, between November 2015 and June 2016 in Kinshasa, Democratic Republic of Congo. Serological and molecular diagnostic tests for selected arboviral infections were performed on blood, including PCR, NS1-RDT, ELISA and IFA for acute, and ELISA and IFA for past infections.


Investigation among 342 patients, aged 2 to 68 years (mean age of 21 years), with acute undifferentiated fever (having no clear focus of infection) revealed 19 (8.1%) acute dengue–caused by DENV-1 and/or DENV-2 –and 2 (0.9%) acute chikungunya infections. Furthermore, 30.2% and 26.4% of participants had been infected in the past with dengue and chikungunya, respectively. We found no evidence of acute Zika nor yellow fever virus infections. 45.3% of patients tested positive on malaria Rapid Diagnostic Test, 87.7% received antimalarial treatment and 64.3% received antibacterial treatment.


Chikungunya outbreaks have been reported in the study area in the past, so the high seroprevalence is not surprising. However, scarce evidence exists on dengue transmission in Kinshasa and based on our data, circulation is more important than previously reported. Furthermore, our study shows that the prescription of antibiotics, both antibacterial and antimalarial drugs, is rampant. Studies like this one, elucidating the causes of acute fever, may lead to a more considerate and rigorous use of antibiotics. This will not only stem the ever-increasing problem of antimicrobial resistance, but will–ultimately and hopefully–improve the clinical care of outpatients in low-resource settings.

Trial registration NCT02656862.


Author summary

Malaria remains one of the most important causes of fever in sub-Saharan Africa. However, its share is declining, since the diagnosis and treatment of malaria have improved significantly over the years. Hence leading to an increase in the number of patients presenting with non-malarial fever. Often, obvious clinical signs and symptoms like cough or diarrhea are absent, probing the question: “What causes the fever?” Previous studies have shown that the burden of arboviral infections–like dengue and chikungunya–in sub-Saharan Africa is underestimated, which is why we screened for four common arboviral infections in patients presenting with ‘undifferentiated fever’ at an outpatient clinic in suburban Kinshasa, Democratic Republic of Congo. Among the patients tested, we found that one in ten presented with an acute arboviral infection and that almost one in three patients had been infected in the past. These findings suggest that clinicians should think about arboviral infections more often, thereby refraining from the prescription of antibiotics, a practice increasingly problematic given the global rise of antimicrobial resistance.


Citation: Proesmans S, Katshongo F, Milambu J, Fungula B, Muhindo Mavoko H, Ahuka-Mundeke S, et al. (2019) Dengue and chikungunya among outpatients with acute undifferentiated fever in Kinshasa, Democratic Republic of Congo: A cross-sectional study. PLoS Negl Trop Dis 13(9): e0007047.

Editor: Stuart D. Blacksell, Mahidol Univ, Fac Trop Med, THAILAND

Received: November 28, 2018; Accepted: August 6, 2019; Published: September 5, 2019

Copyright: © 2019 Proesmans et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are within the manuscript and its Supporting Information files.

Funding: This study was co-funded by the framework agreement between the Institute of Tropical Medicine and the Belgian development cooperation ( to VV and Vlaamse Interuniversitaire Raad – Universitaire Ontwikkelingssamenwerking ( (VLIR-UOS, Grant reference ZRDC2014MP083) to JPVG. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

Keywords: Arbovirus; Dengue fever; Chikungunya fever; Malaria; Serology; Seroprevalence; DRC.


Decreased #humoral #immunity to #mumps in young #adults immunized with #MMR #vaccine in #childhood (Proc Natl Acad Sci USA, abstract)

[Source: Proceedings of the National Academy of Sciences of the United States of America, full page: (LINK). Abstract, edited.]

Decreased humoral immunity to mumps in young adults immunized with MMR vaccine in childhood

Mohammed Ata Ur Rasheed, Carole J. Hickman, Marcia McGrew, Sun Bae Sowers, Sara Mercader, Amy Hopkins, Vickie Grimes, Tianwei Yu, Jens Wrammert, Mark J. Mulligan, William J. Bellini, Paul A. Rota, Walter A. Orenstein, Rafi Ahmed, and Srilatha Edupuganti

PNAS first published September 3, 2019 / DOI:

Contributed by Rafi Ahmed, July 18, 2019 (sent for review April 2, 2019; reviewed by Rino Rappuoli and Robert Seder)



The live-attenuated mumps-measles-rubella (MMR) vaccine has been highly successful in the United States since its introduction 47 years ago. However, for the past decade, mumps outbreaks have been occurring among young adults who were vaccinated as children. Waning immunity has been proposed as a key contributing factor to mumps resurgence. In our sample (n = 71) of 18- to 23-year-old college students, the majority had detectable mumps IgG antibodies by enzyme-linked immunosorbent assay (ELISA) but the magnitude was lower than rubella. Neutralizing antibody titers were 6-fold lower to a circulating genotype G mumps strain versus the vaccine strain. Ten percent of our participants had no detectable memory B cells to mumps. Strategies are needed to improve immunity to the mumps vaccine.



In the past decade, multiple mumps outbreaks have occurred in the United States, primarily in close-contact, high-density settings such as colleges, with a high attack rate among young adults, many of whom had the recommended 2 doses of mumps-measles-rubella (MMR) vaccine. Waning humoral immunity and the circulation of divergent wild-type mumps strains have been proposed as contributing factors to mumps resurgence. Blood samples from 71 healthy 18- to 23-year-old college students living in a non-outbreak area were assayed for antibodies and memory B cells (MBCs) to mumps, measles, and rubella. Seroprevalence rates of mumps, measles, and rubella determined by IgG enzyme-linked immunosorbent assay (ELISA) were 93, 93, and 100%, respectively. The index standard ratio indicated that the concentration of IgG was significantly lower for mumps than rubella. High IgG avidity to mumps Enders strain was detected in sera of 59/71 participants who had sufficient IgG levels. The frequency of circulating mumps-specific MBCs was 5 to 10 times lower than measles and rubella, and 10% of the participants had no detectable MBCs to mumps. Geometric mean neutralizing antibody titers (GMTs) by plaque reduction neutralization to the predominant circulating wild-type mumps strain (genotype G) were 6-fold lower than the GMTs against the Jeryl Lynn vaccine strain (genotype A). The majority of the participants (80%) received their second MMR vaccine ≥10 years prior to study participation. Additional efforts are needed to fully characterize B and T cell immune responses to mumps vaccine and to develop strategies to improve the quality and durability of vaccine-induced immunity.

mumps, measles, rubella – MMR vaccine – memory B cells (MBCs) – plaque reduction  -neutralization titers – IgG ELISA



1 To whom correspondence may be addressed. Email: or

Author contributions: M.A.U.R., C.J.H., W.J.B., W.A.O., R.A., J.W., and S.E. designed research; M.A.U.R., C.J.H., M.M., S.B.S., S.M., A.H., V.G., and S.E. performed research; M.A.U.R., C.J.H., S.B.S., S.M., T.Y., and S.E. analyzed data; and M.A.U.R., C.J.H., J.W., M.J.M., W.J.B., P.A.R., W.A.O., R.A., and S.E. wrote the paper.

Reviewers: R.R., GlaxoSmithKline; and R.S., NIH.

The authors declare no conflict of interest.

This article contains supporting information online at

Published under the PNAS license.

Keywords: Mumps; Vaccines; Serology; Seroprevalence; Immunoglobulins.


#Enterovirus D68 #serosurvey: evidence for #endemic circulation in the #Netherlands, 2006 to 2016 (Euro Surveill., abstract)

[Source: Eurosurveillance, full page: (LINK). Abstract, edited.]

Enterovirus D68 serosurvey: evidence for endemic circulation in the Netherlands, 2006 to 2016

Eveliina Karelehto1, Gerrit Koen1, Kimberley Benschop2, Fiona van der Klis2, Dasja Pajkrt3, Katja Wolthers1

Affiliations: 1 Department of Medical Microbiology, Laboratory of Clinical Virology, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands; 2 National Institute for Public Health and the Environment, Bilthoven, the Netherlands; 3 Department of Pediatric Infectious Diseases, Emma Children’s Hospital, University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands

Correspondence:  Katja C Wolthers

Citation style for this article: Karelehto Eveliina, Koen Gerrit, Benschop Kimberley, van der Klis Fiona, Pajkrt Dasja, Wolthers Katja. Enterovirus D68 serosurvey: evidence for endemic circulation in the Netherlands, 2006 to 2016. Euro Surveill. 2019;24(35):pii=1800671.

Received: 12 Dec 2018;   Accepted: 05 Jun 2019




Enterovirus D68 (EV-D68) has caused major outbreaks of severe respiratory illness worldwide since 2010.


Our aim was to evaluate EV-D68 circulation in the Netherlands by conducting a serosurvey of EV-D68 neutralising antibodies (nAb) among the Dutch general population.


We screened 280 sera from children and adults in the Netherlands and used two independent sets of samples collected in the years 2006 and 2007 and in the years 2015 and 2016, time points before and after the first EV-D68 upsurge in 2010. Neutralisation capacity of the sera was tested against the prototype Fermon EV-D68 strain isolated in 1962 and against a recent EV-D68 strain (genotype B3) isolated in France in 2016.


Regardless of the time of serum collection, we found remarkably high overall seropositivity (94.3–98.3%) for nAb against both EV-D68 strains. Geometric mean titres increased in an age-dependent manner.


Our data suggest that EV-D68 has been circulating in the Netherlands for decades and that the enterovirus surveillance does not accurately capture the prevalence of this clinically relevant pathogen.

©  This work is licensed under a Creative Commons Attribution 4.0 International License.

Keywords: Enterovirus; EV-D68; Pediatrics; Netherlands; Seroprevalence.


Comparison of #Serologic #Assays for #MERS #Coronavirus (Emerg Infect Dis., abstract)

[Source: US Centers for Disease Control and Prevention (CDC), Emerging Infectious Diseases Journal, full page: (LINK). Abstract, edited.]

Volume 25, Number 10—October 2019 / Research

Comparison of Serologic Assays for Middle East Respiratory Syndrome Coronavirus

Ruth Harvey, Giada Mattiuzzo  , Mark Hassall, Andrea Sieberg, Marcel A. Müller, Christian Drosten, Peter Rigsby, Christopher J. Oxenford, and study participants

Author affiliations: National Institute for Biological Standards and Control—MHRA, Potters Bar, UK (R. Harvey, G. Mattiuzzo, M. Hassall, P. Rigsby); Charité-Universitätsmedizin Berlin, Berlin, Germany (A. Sieberg, M.A. Müller, C. Drosten); Humboldt-Universität zu Berlin, Berlin (A. Sieberg, M.A. Müller, C. Drosten); Berlin Institute of Health, Berlin (A. Sieberg, M.A. Müller, C. Drosten); German Centre for Infection Research, Berlin (M.A. Müller, C. Drosten); World Health Organization, Lyon, France (C.J. Oxenford).



Middle East respiratory syndrome coronavirus (MERS-CoV) was detected in humans in 2012. Since then, sporadic outbreaks with primary transmission through dromedary camels to humans and outbreaks in healthcare settings have shown that MERS-CoV continues to pose a threat to human health. Several serologic assays for MERS-CoV have been developed globally. We describe a collaborative study to investigate the comparability of serologic assays for MERS-CoV and assess any benefit associated with the introduction of a standard reference reagent for MERS-CoV serology. Our study findings indicate that, when possible, laboratories should use a testing algorithm including >2 tests to ensure correct diagnosis of MERS-CoV. We also demonstrate that the use of a reference reagent greatly improves the agreement between assays, enabling more consistent and therefore more meaningful comparisons between results.

Keywords: MERS-CoV; Serology; Diagnostic tests.


Sensitive and Specific #Detection of Low-Level #Antibody Responses in Mild #MERS #Coronavirus #Infections (Emerg Infect Dis., abstract)

[Source: US Centers for Disease Control and Prevention (CDC), Emerging Infectious Diseases Journal, full page: (LINK). Abstract, edited.]

Volume 25, Number 10—October 2019 / Research

Sensitive and Specific Detection of Low-Level Antibody Responses in Mild Middle East Respiratory Syndrome Coronavirus Infections

Nisreen M.A. Okba, V. Stalin Raj, Ivy Widjaja, Corine H. Geurts van Kessel, Erwin de Bruin, Felicity D. Chandler, Wan Beom Park, Nam-Joong Kim, Elmoubasher A.B.A. Farag, Mohammed Al-Hajri, Berend-Jan Bosch, Myoung-don Oh, Marion P.G. Koopmans, Chantal B.E.M. Reusken, and Bart L. Haagmans

Author affiliations: Erasmus Medical Center, Rotterdam, the Netherlands (N.M.A. Okba, V.S. Raj, C.H. Geurts van Kessel, E. de Bruin, F.D. Chandler, M.P.G. Koopmans, C.B.E.M. Reusken, B.L. Haagmans); Utrecht University, Utrecht, the Netherlands (I. Widjaja, B.-J. Bosch); Seoul National University College of Medicine, Seoul, South Korea (W.B. Park, N.-J. Kim, M.-D. Oh); Ministry of Public Health, Doha, Qatar (E.A.B.A. Farag, M. Al-Hajri)



Middle East respiratory syndrome coronavirus (MERS-CoV) infections in humans can cause asymptomatic to fatal lower respiratory lung disease. Despite posing a probable risk for virus transmission, asymptomatic to mild infections can go unnoticed; a lack of seroconversion among some PCR-confirmed cases has been reported. We found that a MERS-CoV spike S1 protein–based ELISA, routinely used in surveillance studies, showed low sensitivity in detecting infections among PCR-confirmed patients with mild clinical symptoms and cross-reactivity of human coronavirus OC43–positive serum samples. Using in-house S1 ELISA and protein microarray, we demonstrate that most PCR-confirmed MERS-CoV case-patients with mild infections seroconverted; nonetheless, some of these samples did not have detectable levels of virus-neutralizing antibodies. The use of a sensitive and specific serologic S1-based assay can be instrumental in the accurate estimation of MERS-CoV prevalence.

Keywords: MERS-CoV; Serology; Seroprevalence.