#Antibody levels in a cohort of #pregnant women after the #influenza A #H1N1pdm09 #pandemic: waning and association with self-reported severity and duration of illness (Influenza Other Respir Viruses, abstract)

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

Influenza Other Respir Viruses. 2018 Dec 9. doi: 10.1111/irv.12623. [Epub ahead of print]

Antibody levels in a cohort of pregnant women after the 2009 influenza A(H1N1) pandemic: waning and association with self-reported severity and duration of illness.

Tunheim G1,2, Laake I1, Robertson AH1, Waalen K1, Hungnes O1, Naess LM1, Cox RJ2,3,4, Mjaaland S1,2, Trogstad L1.

Author information: 1 Division of Infection Control and Environmental Health, Norwegian Institute of Public Health, 0213, Oslo, Norway. 2 K. G. Jebsen Centre for Influenza Vaccine Research, University of Oslo, 0424, Oslo, Norway. 3 The Influenza Centre, Department of Clinical Science, University of Bergen, 5021, Bergen, Norway. 4 Department of Research and Development, Haukeland University Hospital, N5021, Bergen, Norway.




A population-based pregnancy cohort was established in Norway to study potential effects of exposure to the 2009 influenza pandemic or pandemic vaccination during pregnancy.


We studied maternal A(H1N1)pdm09-specific hemagglutination inhibition (HI)-titer levels and waning in women with influenza-like illness (ILI) in pregnancy compared to vaccinated women. Moreover, we studied the association between HI-titers and self-reported severity and duration of ILI.


HI-titers against the pandemic virus were measured in maternal blood samples obtained at birth, 3-9 months after exposure, and linked with information about pregnancy, influenza and vaccination from national registries and a cohort questionnaire.


Among 1821 pregnant women included, 43.7% were unvaccinated and 19.3% of these had ILI. HI-titers were low (geometric mean titer (GMT) 11.3) in the unvaccinated women with ILI. Higher HI-titers (GMT 37.8) were measured in the vaccinated women. Estimated HI-titer waning was similar for vaccinated women and women with ILI. Most ILI episodes were moderate and lasted 3-5 days. Women with ILI reporting specific influenza symptoms such as fever or cough had higher HI-titers than women without these symptoms. Women who reported being “very ill” or illness duration of >5 days, had higher HI-titers than women reporting less severe illness or illness of shorter duration, respectively.


Antibody waning was similar in vaccinated women and women with ILI. More severe ILI or longer duration of illness were associated with higher HI-titers. Most unvaccinated pregnant women with ILI had low HI-titers, probably due to moderate illness and HI-titer waning between exposure and sampling.

This article is protected by copyright. All rights reserved.

KEYWORDS: antibodies; influenza; pandemic H1N1pdm09; pregnancy; vaccination; waning

PMID: 30536590 DOI: 10.1111/irv.12623

Keywords: Pandemic Influenza; H1N1pdm09; Vaccines; Pregnancy.



#Influenza and #Pregnancy: No Time for #Complacency (Obstet Gynecol., abstract)

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

Obstet Gynecol. 2018 Dec 4. doi: 10.1097/AOG.0000000000003040. [Epub ahead of print]

Influenza and Pregnancy: No Time for Complacency.

Rasmussen SA1, Jamieson DJ.

Author information: 1 University of Florida College of Medicine & College of Public Health and Health Professions, Departments of Pediatrics and Epidemiology, Gainesville, Florida; and Emory University, Department of Gynecology and Obstetrics, Atlanta, Georgia.



The 2009 H1N1 pandemic demonstrated the severe effects of influenza illness on pregnant women. This experience stimulated efforts to improve influenza vaccination coverage among pregnant women and resulted in a substantial increase in coverage from less than 30% before 2009 to more than 50% a few years later. As memories fade of the pandemic year, influenza vaccination coverage has stagnated at around 50%, despite considerable information becoming available on strategies to improve vaccination coverage during pregnancy. The American College of Obstetricians and Gynecologists, through its expert work groups, Committee Opinions, and other outreach efforts, has provided strong support for clinicians to implement these strategies into their practices. Influenza vaccination is the best way to safeguard pregnant women and their infants up to 6 months of age from the adverse outcomes associated with influenza. It is imperative for the obstetric community to redouble its efforts to implement strategies proven to work to improve vaccination coverage and to identify and test new strategies to increase the number of pregnant women and their infants protected from influenza.

PMID: 30531576 DOI: 10.1097/AOG.0000000000003040

Keywords: Pandemic Influenza; H1N1pdm09; Vaccines; Pregnancy.


#Seroprevalence of #Zika virus among asymptomatic #pregnant mothers and their #newborns in the #Najran region of southwest #Saudi Arabia (Ann Saudi Med., abstract)

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

Ann Saudi Med. 2018 Nov-Dec;38(6):408-412. doi: 10.5144/0256-4947.2018.408.

Seroprevalence of Zika virus among asymptomatic pregnant mothers and their newborns in the Najran region of southwest Saudi Arabia.

Alayed MS, Qureshi MA, Ahmed S, Alqahtani AS, Al-Qahtani AM, Alshaybari K, Alshahrani M, Asaad AM.




Zika virus (ZIKV) is a teratogenic flavivirus that can cause microcephaly. Its main vector, Aedes aegypti, has been previ.ously identified in Saudi Arabia, but no ZIKV infection has yet been reported. Nevertheless, the country is at risk from ZIKV because it receives many travelers throughout the year, including pilgrims from ZIKV-endemic countries.


Screen asymptomatic pregnant mothers and their newborns attending a major hospital in the Najran region for subclinical or past infections with ZIKV, using ELISA and RT-PCR.




Najran Maternity and Children Hospital (NMCH).


All pregnant women admitted to NMCH in labor between November 2016 and July 2017 were included in the study. Clinical and demographic data were collected by pre-validated physician-administered questionnaires. Paired umbilical and maternal serum samples were collected and frozen at -60°C, using ELISA to measure anti-ZIKA IgG and IgM antibodies and RT-PCR to further investigate positive samples.


Maternal and newborn serum anti-ZIKV IgM and IgG and ZIKV RT-PCR.


410 mother-newborn pairs.


The median gestational age was 38.5 weeks (range 33-42). Most (n=342, 83.41%) of the women were from Najran city. All of the newborns had normal growth parameters with no congenital malformations. None of the mothers had symptoms suggestive of ZIKV infection; 3 (0.7%) exhibited a low-grade fever (38°C), but did not test positive for anti-ZIKV antibodies. Thirty-five (8.53%) of mothers had travelled inside Saudi Arabia, but none outside the country. Twenty-four (5.85%) mothers tested positive for anti-ZIKV IgM and 52 (12.68%) tested positive for anti-ZIKV IgG, but all infant samples were negative. All seropositive ZIKV IgM were also ZIKV IgG positive, but RT-PCR test.ing of all seropositive samples was negative.


Although previous (resolved) ZIKV infection and cross-reactivity of the ELISA method with other flaviviruses cannot be ex.cluded, the study found no confirmed cases of acute ZIKV infection. However, given the presence of the vector in Saudi Arabia, the presence of presumptive positive serology and the ongoing risk of ZIKV entry via a regular influx of travelers from endemic areas, we propose that continuous surveillance be conducted for ZIKV as well for other flaviviruses. Larger-scale nationwide studies are strongly recommended to gain a broader view of the potential threat from ZIKV in the country.


Small sample size, unavailability of plaque reduction neutralization tests to confirm serology results, and RT-PCR was only conducted on ELISA-positive serum samples, due to resource constraints.


PMID: 30531174 DOI: 10.5144/0256-4947.2018.408

Keywords: Saudi Arabia; Zika Virus; Zika Congenital Infection; Seroprevalence; Pregnancy.


Potential inconsistencies in [#Zika #surveillance data and our understanding of #risk during #pregnancy (PLoS Negl Trop Dis., abstract)

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


Potential inconsistencies in Zika surveillance data and our understanding of risk during pregnancy

James A. Hay, Pierre Nouvellet, Christl A. Donnelly, Steven Riley

Published: December 10, 2018 / DOI: https://doi.org/10.1371/journal.pntd.0006991 / This is an uncorrected proof.




A significant increase in microcephaly incidence was reported in Northeast Brazil at the end of 2015, which has since been attributed to an epidemic of Zika virus (ZIKV) infections earlier that year. Further incidence of congenital Zika syndrome (CZS) was expected following waves of ZIKV infection throughout Latin America; however, only modest increases in microcephaly and CZS incidence have since been observed. The quantitative relationship between ZIKV infection, gestational age and congenital outcome remains poorly understood.

Methodology/Principle findings

We characterised the gestational-age-varying risk of microcephaly given ZIKV infection using publicly available incidence data from multiple locations in Brazil and Colombia. We found that the relative timings and shapes of ZIKV infection and microcephaly incidence curves suggested different gestational risk profiles for different locations, varying in both the duration and magnitude of gestational risk. Data from Northeast Brazil suggested a narrow window of risk during the first trimester, whereas data from Colombia suggested persistent risk throughout pregnancy. We then used the model to estimate which combination of behavioural and reporting changes would have been sufficient to explain the absence of a second microcephaly incidence wave in Bahia, Brazil; a population for which we had two years of data. We found that a 18.9-fold increase in ZIKV infection reporting rate was consistent with observed patterns.


Our study illustrates how surveillance data may be used in principle to answer key questions in the absence of directed epidemiological studies. However, in this case, we suggest that currently available surveillance data are insufficient to accurately estimate the gestational-age-varying risk of microcephaly from ZIKV infection. The methods used here may be of use in future outbreaks and may help to inform improved surveillance and interpretation in countries yet to experience an outbreak of ZIKV infection.


Author summary

Zika virus (ZIKV) infection is associated with the rise of microcephaly cases observed in Northeast Brazil at the end of 2015. For women in endemic or at-risk areas, understanding how the relationship between time of infection and microcephaly risk varies through pregnancy is important in informing family planning. However, a relatively modest number of congenital Zika syndrome cases have been observed following subsequent waves of ZIKV infection, limiting our understanding of gestational risk. We used a mathematical model to quantify the shape and magnitude of the gestational-age-varying risk to a fetus. Although the risk profile should be conserved regardless of location, we estimated different profiles when using surveillance data from locations in Northeast Brazil and Colombia. Our results suggest that time-dependent reporting changes likely confound the interpretation of currently available surveillance data. Furthermore, we investigated a range of behavioural and reporting rate changes that could explain two waves of ZIKV infection in Bahia, Brazil despite only one wave of microcephaly. Plausible changes in reporting could explain these data whilst remaining consistent with the hypothesis that ZIKV infection carries a significant risk of microcephaly. Further evidence is needed to disentangle the true risk of congenital Zika syndrome from time-varying reporting changes.


Citation: Hay JA, Nouvellet P, Donnelly CA, Riley S (2018) Potential inconsistencies in Zika surveillance data and our understanding of risk during pregnancy. PLoS Negl Trop Dis 12(12): e0006991. https://doi.org/10.1371/journal.pntd.0006991

Editor: Ernesto T. A. Marques, University of Pittsburgh, UNITED STATES

Received: June 29, 2017; Accepted: November 12, 2018; Published: December 10, 2018

Copyright: © 2018 Hay 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 files are available and embedded within the accompanying github repository https://github.com/jameshay218/zikaInfer.

Funding: For funding, we thank: The Wellcome Trust www.wellcome.ac.uk (Investigator Award, 200861/Z/16/Z, SR); The Medical Research Council, UK (www.mrc.ac.uk, JAH, SR, PN, CAD); National Institute for Health Research HPRU (SR, CAD, PN). 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: Zika Virus; Zika Congenital infection; Pregnancy.


#Vitamin A #Supplementation during #Pregnancy Enhances #H1N1pdm09 #Vaccine Response in #Mothers, but Enhancement of Transplacental #Antibody Transfer May Depend on When Mothers Are Vaccinated during Pregnancy (J Nutr., abstract)

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

J Nutr. 2018 Dec 1;148(12):1968-1975. doi: 10.1093/jn/nxy228.

Vitamin A Supplementation during Pregnancy Enhances Pandemic H1N1 Vaccine Response in Mothers, but Enhancement of Transplacental Antibody Transfer May Depend on When Mothers Are Vaccinated during Pregnancy.

Ahmad SM1, Alam MJ1, Khanam A1, Rashid M1, Islam S1, Kabir Y2, Raqib R1, Steinhoff MC3.

Author information: 1 Infectious Diseases Division, International Center for Diarrheal Disease Research, Bangladesh (icddr,b), Mohakhali, Dhaka, Bangladesh. 2 Department of Biochemistry and Molecular Biology, University of Dhaka, Dhaka, Bangladesh. 3 Global Health Center, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH.




In the growing embryo, the vitamin A requirement is tightly regulated. Maternal vitamin A deficiency during pregnancy may alter maternal immune function to accommodate the fetus.


Our primary objective was to determine the effect of oral vitamin A supplementation (VAS) during pregnancy and until 6 mo postpartum on pandemic H1N1-vaccine responses in mothers and their infants at 6 mo of age.


In this randomized controlled clinical trial, pregnant women (n = 112) during the second trimester (mean ± SD: 14 ± 1 wk) were assigned to receive either an oral dose of 10,000 IU vitamin A or placebo weekly until 6 mo postpartum. During the third trimester, mothers received a single dose of inactivated pandemic H1N1-influenza vaccine. Hemagglutination-inhibition (HAI) titer was measured in cord, infant, and maternal blood samples. Multivariate regressions with adjustments were used for data analysis.


Seventy-six percent of women had low plasma retinol concentrations (<1.05 μmol/L) in their second trimester. VAS of mothers increased vitamin A concentrations in cord blood by 21.4% and in colostrum by 40.7%. At 6 mo postpartum, women in the vitamin A group had 38.7% higher HAI titers and a higher proportion of HAI titer of ≥1:40 of the cutoff compared with the placebo group. A total of 54.5% of infants had an HAI titer ≥1:40 at 6 mo of age, but there was no difference in HAI titer in infants between groups. Overall, HAI in cord blood did not differ between groups, but in the placebo group, cord blood HAI was negatively associated with maternal “vaccination-to-delivery intervals” (rs = -0.401; P = 0.5), and maternal VAS increased cord blood HAI 6-fold if antenatal immunization was administered ≥10 wk before delivery.


In a community with low vitamin A status, weekly maternal VAS during pregnancy and postpartum increases the breast-milk vitamin A concentration and enhances prenatal H1N1-vaccine responses in mothers, but the benefits of maternal VAS in transplacental antibody transfer may depend on the time of gestation when mothers were vaccinated. This trial was registered at clinicaltrials.gov as NCT00817661.

PMID: 30517724 DOI: 10.1093/jn/nxy228

Keywords: Seasonal Influenza; H1N1pdm09; Vitamin A; Vaccines; Pregnancy.


#Pregnant Women and the #Ebola #Crisis (N Engl J Med., summary)

[Source: The New England Journal of Medicine, full page: (LINK). Summary, edited.]


Pregnant Women and the Ebola Crisis

Lisa B. Haddad, M.D., M.P.H., Denise J. Jamieson, M.D., M.P.H., and Sonja A. Rasmussen, M.D.


On August 1, 2018, the Ministry of Health of the Democratic Republic of Congo (DRC) reported the emergence of another Ebola virus outbreak, the 10th in the DRC since the virus was discovered in 1976. As of November 13, 2018, there were 341 cases and 215 deaths, making this the world’s third-largest Ebola outbreak to date.1 The public health community learned several lessons when West Africa experienced the largest-ever Ebola outbreak beginning in 2014, which ultimately included 28,000 cases and caused 11,000 deaths. Current prevention and control measures have benefited from these lessons and are directed toward a coordinated response, including improvements in cross-border surveillance, laboratory capacity, case management, infection control at health facilities, culturally sensitive safe burials, and psychosocial care, as well as inclusion of vaccination as a control measure. However, according to available documents, issues related to pregnant women have been largely ignored in these efforts.



Disclosure forms provided by the authors are available at NEJM.org.

This article was published on November 28, 2018, at NEJM.org.

Author Affiliations: From the Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta (L.B.H, D.J.J.); and the Departments of Pediatrics and Epidemiology, University of Florida College of Medicine and College of Public Health and Health Professions, Gainesville (S.A.R.).

Keywords: Ebola; Pregnancy.


Cross-Reactive #Dengue Virus #Antibodies Augment #Zika Virus #Infection of #Human #Placental Macrophages (Cell Host Microbe, abstract)

[Source: Cell Host Microbe, full page: (LINK). Abstract, edited.]

Cross-Reactive Dengue Virus Antibodies Augment Zika Virus Infection of Human Placental Macrophages

Matthew G. Zimmerman 8, Kendra M. Quicke 8, Justin T. O’Neal, Nitin Arora, Deepa Machiah, Lalita Priyamvada, Robert C. Kauffman, Emery Register, Oluwaseyi Adekunle, Dominika Swieboda, Erica L. Johnson, Sarah Cordes, Lisa Haddad, Rana Chakraborty, Carolyn B. Coyne, Jens Wrammert, Mehul S. Suthar 9

Published: November 14, 2018 / DOI: https://doi.org/10.1016/j.chom.2018.10.008



  • Cross-reactive DENV antibodies enhance ZIKV infection in human Hofbauer cells
  • Enhanced ZIKV infection in mid-gestation explants is IgG subclass dependent
  • ZIKV immune complexes target Hofbauer cells within the villous stroma



Zika virus (ZIKV), which emerged in regions endemic to dengue virus (DENV), is vertically transmitted and results in adverse pregnancy outcomes. Antibodies to DENV can cross-react with ZIKV, but whether these antibodies influence ZIKV vertical transmission remains unclear. Here, we find that DENV antibodies increase ZIKV infection of placental macrophages (Hofbauer cells [HCs]) from 10% to over 80% and enhance infection of human placental explants. ZIKV-anti-DENV antibody complexes increase viral binding and entry into HCs but also result in blunted type I interferon, pro-inflammatory cytokine, and antiviral responses. Additionally, ZIKV infection of HCs and human placental explants is enhanced in an immunoglobulin G subclass-dependent manner, and targeting FcRn reduces ZIKV replication in human placental explants. Collectively, these findings support a role for pre-existing DENV antibodies in enhancement of ZIKV infection of select placental cell types and indicate that pre-existing immunity to DENV should be considered when addressing ZIKV vertical transmission.

Keywords: Zika virus – placental macrophages – antibody-dependent enhancement – dengue virus – cross-reactive antibodies – type I interferon – vertical transmission

Keywords: Zika Virus; Dengue Fever; Pregnancy; ADE; Animal models.