Ongoing Measles in the Developed and Developing World.

Measles is a vaccine-preventable illness. Nevertheless, in recent years, measles is still endemic and epidemic in both the developed world and the developing world. The public perception of measles in the past was that it was not a big deal. However, measles is associated with a number of complications which can be places in three categories which are: acute(diarrhea, otitis media, pneumonia, encephalitis, seizures, and death) and delayed-subacute sclerosing panencephalitis (SSPE) and post-measles immune amnesia. Contrary to the beliefs of the anti-vaccine lobby, measles is bad. In acute measles, the death rate is 1-3 per 1000 and the risk of encephalitis is 1 per 1000. Relatively recent investigations indicate that SSPE is considerably more common than previously believed. The worldwide contribution of post-measles immune amnesia to morbidity and mortality is likely to be huge. In exposure situations, two doses of measles vaccine will prevent 99% of cases. Presently in the United States, the first dose is given at 12 through 15 months of age. The second dose is most often administered at 4 through 6 years of age. In my opinion, the second dose of measles vaccine should be given 4-6 weeks after the first dose rather than at 4-6 years of age. Children who don't have antibody to measles should not travel to risk areas.

SARS-CoV-2 IgG Spike antibody levels and avidity in natural infection or following vaccination with mRNA-1273 or BNT162b2 vaccines.

Certain aspects of the immunogenicity and effectiveness of the messenger ribonucleic acid (mRNA) vaccines (mRNA-1273 and BNT162b2) developed in response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic are still uncharacterized. Serum or plasma samples from healthy donor recipients of either vaccine (BNT162b2 n = 53, mRNA-1273 n = 49; age 23-67), and individuals naturally infected with SARS-CoV-2 (n = 106; age 18-82) were collected 0-2 months post-infection or 1- and 4 months after second dose of vaccination. Anti-Spike antibody levels and avidity were measured via an enzyme-linked immunosorbent assay (ELISA). Overall, vaccination induced higher circulating anti-Spike protein immunoglobulin G (IgG) antibody levels and avidity compared to infection at similar time intervals. Both vaccines produced similar anti-Spike IgG concentrations at 1 month, while mRNA-1273 demonstrated significantly higher circulating antibody concentrations after 4 months. mRNA-1273 induced significantly higher avidity at month 1 compared to BNT162b2 across all age groups. However, the 23-34 age group was the only group to maintain statistical significance by 4 months. Male BNT162b2 recipients were approaching statistically significant lower anti-Spike IgG avidity compared to females by month 4. These findings demonstrate enhanced anti-Spike IgG levels and avidity following vaccination compared to natural infection. In addition, the mRNA-1273 vaccine induced higher antibody levels by 4 months compared to BNT162b2.

Assay Harmonization Study To Measure Immune Response to SARS-CoV-2 Infection and Vaccines: a Serology Methods Study.

The Coronavirus disease 2019 (COVID-19) pandemic presented the scientific community with an immediate need for accurate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serology assays, resulting in an expansion of assay development, some without following a rigorous quality control and validation, and with a wide range of performance characteristics. Vast amounts of data have been gathered on SARS-CoV-2 antibody response; however, performance and ability to compare the results have been challenging. This study seeks to analyze the reliability, sensitivity, specificity, and reproducibility of a set of widely used commercial, in-house, and neutralization serology assays, as well as provide evidence for the feasibility of using the World Health Organization (WHO) International Standard (IS) as a harmonization tool. This study also seeks to demonstrate that binding immunoassays may serve as a practical alternative for the serological study of large sample sets in lieu of expensive, complex, and less reproducible neutralization assays. In this study, commercial assays demonstrated the highest specificity, while in-house assays excelled in antibody sensitivity. As expected, neutralization assays demonstrated high levels of variability but overall good correlations with binding immunoassays, suggesting that binding may be reasonably accurate as well as practical for the study of SARS-CoV-2 serology. All three assay types performed well after WHO IS standardization. The results of this study demonstrate there are high performing serology assays available to the scientific community to rigorously dissect antibody responses to infection and vaccination. IMPORTANCE Previous studies have shown significant variability in SARS-CoV-2 antibody serology assays, highlighting the need for evaluation and comparison of these assays using the same set of samples covering a wide range of antibody responses induced by infection or vaccination. This study demonstrated that there are high performing assays that can be used reliably to evaluate immune responses to SARS-CoV-2 in the context of infection and vaccination. This study also demonstrated the feasibility of harmonizing these assays against the International Standard and provided evidence that the binding immunoassays may have high enough correlation with the neutralization assays to serve as a practical proxy. These results represent an important step in standardizing and harmonizing the many different serological assays used to evaluate COVID-19 immune responses in the population.

Reported History of Measles and Long-term Impact on Tetanus Antibody Detected in Children 9-59 Months of Age and Receiving 3 Doses of Tetanus Vaccine in the Democratic Republic of the Congo.

BACKGROUND: Recent studies suggest measles-induced immune amnesia could have long-term immunosuppressive effects via preferential depletion of memory CD150+ lymphocytes, and associations with a 2-3 year period of increased mortality and morbidity from infectious diseases other than measles has been shown in children from wealthy and low-income countries. To further examine the associations previous measles virus infection may have on immunologic memory among children in the Democratic Republic of the Congo (DRC), we assessed tetanus antibody levels among fully vaccinated children, with and without a history of measles. METHODS: We assessed 711 children 9-59 months of age whose mothers were selected for interview in the 2013-2014 DRC Demographic and Health Survey. History of measles was obtained by maternal report and classification of children who had measles in the past was completed using maternal recall and measles IgG serostatus obtained from a multiplex chemiluminescent automated immunoassay dried blood spot analysis. Tetanus IgG antibody serostatus was similarly obtained. A logistic regression model was used to identify association of measles and other predictors with subprotective tetanus IgG antibody. RESULTS: Subprotective geometric mean concentration tetanus IgG antibody values were seen among fully vaccinated children 9-59 months of age, who had a history of measles. Controlling for potential confounding variables, children classified as measles cases were less likely to have seroprotective tetanus toxoid antibody (odds ratio: 0.21; 95% confidence interval: 0.08-0.55) compared with children who had not had measles. CONCLUSIONS: History of measles was associated with subprotective tetanus antibody among this sample of children in the DRC who were 9-59 months of age and fully vaccinated against tetanus.

A Trans-Governmental Collaboration to Independently Evaluate SARS-CoV-2 Serology Assays.

The emergence of SARS-CoV-2 created a crucial need for serology assays to detect anti-SARS-CoV-2 antibodies, which led to many serology assays entering the market. A trans-government collaboration was created in April 2020 to independently evaluate the performance of commercial SARS-CoV-2 serology assays and help inform U.S. Food and Drug Administration (FDA) regulatory decisions. To assess assay performance, three evaluation panels with similar antibody titer distributions were assembled. Each panel consisted of 110 samples with positive (n = 30) serum samples with a wide range of anti-SARS-CoV-2 antibody titers and negative (n = 80) plasma and/or serum samples that were collected before the start of the COVID-19 pandemic. Each sample was characterized for anti-SARS-CoV-2 antibodies against the spike protein using enzyme-linked immunosorbent assays (ELISA). Samples were selected for the panel when there was agreement on seropositivity by laboratories at National Cancer Institute's Frederick National Laboratory for Cancer Research (NCI-FNLCR) and Centers for Disease Control and Prevention (CDC). The sensitivity and specificity of each assay were assessed to determine Emergency Use Authorization (EUA) suitability. As of January 8, 2021, results from 91 evaluations were made publicly available (https://open.fda.gov/apis/device/covid19serology/, and https://www.cdc.gov/coronavirus/2019-ncov/covid-data/serology-surveillance/serology-test-evaluation.html). Sensitivity ranged from 27% to 100% for IgG (n = 81), from 10% to 100% for IgM (n = 74), and from 73% to 100% for total or pan-immunoglobulins (n = 5). The combined specificity ranged from 58% to 100% (n = 91). Approximately one-third (n = 27) of the assays evaluated are now authorized by FDA for emergency use. This collaboration established a framework for assay performance evaluation that could be used for future outbreaks and could serve as a model for other technologies. IMPORTANCE The SARS-CoV-2 pandemic created a crucial need for accurate serology assays to evaluate seroprevalence and antiviral immune responses. The initial flood of serology assays entering the market with inadequate performance emphasized the need for independent evaluation of commercial SARS-CoV-2 antibody assays using performance evaluation panels to determine suitability for use under EUA. Through a government-wide collaborative network, 91 commercial SARS-CoV-2 serology assay evaluations were performed. Three evaluation panels with similar overall antibody titer distributions were assembled to evaluate performance. Nearly one-third of the assays evaluated met acceptable performance recommendations, and two assays had EUAs revoked and were removed from the U.S. market based on inadequate performance. Data for all serology assays evaluated are available at the FDA and CDC websites (https://open.fda.gov/apis/device/covid19serology/, and https://www.cdc.gov/coronavirus/2019-ncov/covid-data/serology-surveillance/serology-test-evaluation.html).

Pertussis vaccines.

PURPOSE OF REVIEW: Pertussis is a vaccine preventable cough illness. It can be controlled by universal pertussis vaccination. RECENT FINDINGS: Pertussis cases and deaths in children are at a record low number. More complete use of adolescent/adult vaccine can further reduce morbidity and mortality. SUMMARY: Considerable progress in the control of pertussis has occurred over the last 75 years. The universal use of Tdap vaccines in all pregnant women will prevent virtually all pertussis deaths.

Epidemiology of pertussis in Costa Rica and the impact of vaccination: A 58-year experience (1961-2018).

Costa Rica is an upper middle-income country in Central America with a vigorous public health system. We have studied the number of cases, hospitalizations, and deaths due to pertussis from 1961 to 2018, in relation to vaccine coverage. Following the introduction of the fourth and fifth doses of DTP (booster doses) in 1973 there was a marked reduction of reported pertussis. In 2002 pertussis surveillance and laboratory diagnosis were improved. In 2007, Tdap post-partum immunization was introduced and then switched to intrapartum Tdap immunization in 2011. Of these two strategies post-partum vaccination seemed to have a greater effect in decreasing hospitalizations and deaths, nevertheless, since 2011 there has been only 4 infant deaths due to pertussis.

Antibodies to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in All of Us Research Program Participants, 2 January to 18 March 2020.

BACKGROUND: With limited severe acute respiratory syndrome coronavirus (SARS-CoV-2) testing capacity in the United States at the start of the epidemic (January-March 2020), testing was focused on symptomatic patients with a travel history throughout February, obscuring the picture of SARS-CoV-2 seeding and community transmission. We sought to identify individuals with SARS-CoV-2 antibodies in the early weeks of the US epidemic. METHODS: All of Us study participants in all 50 US states provided blood specimens during study visits from 2 January to 18 March 2020. Participants were considered seropositive if they tested positive for SARS-CoV-2 immunoglobulin G (IgG) antibodies with the Abbott Architect SARS-CoV-2 IgG enzyme-linked immunosorbent assay (ELISA) and the EUROIMMUN SARS-CoV-2 ELISA in a sequential testing algorithm. The sensitivity and specificity of these ELISAs and the net sensitivity and specificity of the sequential testing algorithm were estimated, along with 95% confidence intervals (CIs). RESULTS: The estimated sensitivities of the Abbott and EUROIMMUN assays were 100% (107 of 107 [95% CI: 96.6%-100%]) and 90.7% (97 of 107 [83.5%-95.4%]), respectively, and the estimated specificities were 99.5% (995 of 1000 [98.8%-99.8%]) and 99.7% (997 of 1000 [99.1%-99.9%]), respectively. The net sensitivity and specificity of our sequential testing algorithm were 90.7% (97 of 107 [95% CI: 83.5%-95.4%]) and 100.0% (1000 of 1000 [99.6%-100%]), respectively. Of the 24 079 study participants with blood specimens from 2 January to 18 March 2020, 9 were seropositive, 7 before the first confirmed case in the states of Illinois, Massachusetts, Wisconsin, Pennsylvania, and Mississippi. CONCLUSIONS: Our findings identified SARS-CoV-2 infections weeks before the first recognized cases in 5 US states.

TIPICO XI: report of the first series and podcast on infectious diseases and vaccines (aTIPICO).

TIPiCO is an annual expert meeting and workshop on infectious diseases and vaccination. The edition of 2020 changed its name and format to aTIPiCO, the first series and podcasts on infectious diseases and vaccines. A total of 13 prestigious experts from different countries participated in this edition launched on the 26 November 2020. The state of the art of coronavirus disease-2019 (COVID-19) and the responsible pathogen, the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), and the options to tackle the pandemic situation were discussed in light of the knowledge in November 2020. Despite COVID-19, the status of other infectious diseases, including influenza infections, respiratory syncytial virus disease, human papillomavirus infection, measles, pertussis, tuberculosis, meningococcal disease, and pneumococcal disease, were also addressed. The essential lessons that can be learned from these diseases and their vaccines to use in the COVID-19 pandemic were also commented with the experts.

The influence of exercise intensity and exercise mode on gastrointestinal damage.

Strenuous exercise increases gastrointestinal damage, but the dose-response relationship is yet to be elucidated. It is also commonly believed that running causes greater gastrointestinal damage than cycling. Two randomised, crossover studies aimed to 1) quantify gastrointestinal damage with increasing exercise intensity, and 2) determine if running was associated with greater gastrointestinal damage than cycling. Following a maximal oxygen uptake (V̇O2max) test, participants completed 3 cycling trials at different intensities (60 min at 40%, 60% and 80% V̇O2max; n = 10 (5 female, 5 male)) (INTENSITY), or 1 running and 1 cycling trial (45 min at 70% V̇O2max; n = 11 (3 female, 8 male)) (MODE). Venous blood samples were collected pre- and post-exercise to measure gastrointestinal damage via intestinal fatty acid binding protein (I-FABP). In INTENSITY, I-FABP magnitude of change was greater at 80% V̇O2max than 40% V̇O2max (p < 0.01). In MODE, I-FABP magnitude of change was greater with cycling (mean (SD)) (84.7 (133.2)% d = 1.07) compared with running (19.3 (33.1)%, d = 0.65) with a moderate effect (d = 0.68, p = 0.024). Rating of perceived exertion (RPE) and heart rate (HR) were higher during cycling (RPE p < 0.0001; HR p < 0.0001) but rectal temperature was not different between modes (p = 0.94). While gastrointestinal damage increases with increasing exercise intensity, running was not associated with greater gastrointestinal damage than cycling. Novelty: A fraction of the anaerobic threshold, rather than a fraction of V̇O2max, may be more predictive of intensity that results in exercise induced gastrointestinal damage. The mode of exercise may not be as important as intensity for inducing gastrointestinal damage. Improving anaerobic threshold may reduce susceptibility to gastrointestinal damage when exercising at high intensities.

ZIKA Virus Neutralizing Antibody Kinetics in Antenatally Exposed Infants.

BACKGROUND: Zika virus (ZIKV) is associated with severe congenital abnormalities and laboratory diagnosis of antenatal infection is difficult. Here we evaluated ZIKV neutralizing antibody (nAb) kinetics in infants born to mothers with PCR-confirmed ZIKV infection during pregnancy. METHODS: Neonates (n = 98) had serum specimens tested repeatedly for ZIKV nAb over the first 2 years of life using virus neutralization test (VNT). ZIKV neonatal infection was confirmed by RT-PCR in blood or urine and/or presence of ZIKV IgM antibodies, and results were correlated with infant clinical features. RESULTS: Postnatal laboratory evidence of ZIKV vertical transmission was obtained for 60.2% of children, while 32.7% exhibited clinical abnormalities. Congenital abnormalities were found in 37.3% of children with confirmed ZIKV infection and 31.0% of children without confirmed infection (P = .734). All but 1 child displayed a physiologic decline in ZIKV nAb, reflecting maternal antibody decay, despite an early ZIKV-IgM response in one-third of infants. CONCLUSIONS: Infants with antenatal ZIKV exposure do not develop ZIKV nAb despite an early IgM response. Therefore, ZIKV VNT in children is not useful for diagnosis of congenital infection. In light of these findings, it remains to be determined if children infected in utero are potentially susceptible to reinfection.

Zika virus vertical transmission in children with confirmed antenatal exposure.

We report Zika virus (ZIKV) vertical transmission in 130 infants born to PCR+ mothers at the time of the Rio de Janeiro epidemic of 2015-2016. Serum and urine collected from birth through the first year of life were tested by quantitative reverse transcriptase polymerase chain reaction (PCR) and/or IgM Zika MAC-ELISA. Four hundred and seven specimens are evaluated; 161 sera tested by PCR and IgM assays, 85 urines by PCR. Sixty-five percent of children (N = 84) are positive in at least one assay. Of 94 children tested within 3 months of age, 70% are positive. Positivity declines to 33% after 3 months. Five children are PCR+ beyond 200 days of life. Concordance between IgM and PCR results is 52%, sensitivity 65%, specificity 40% (positive PCR results as gold standard). IgM and serum PCR are 61% concordant; serum and urine PCR 55%. Most children (65%) are clinically normal. Equal numbers of children with abnormal findings (29 of 45, 64%) and normal findings (55 of 85, 65%) have positive results, p = 0.98. Earlier maternal trimester of infection is associated with positive results (p = 0.04) but not clinical disease (p = 0.98). ZIKV vertical transmission is frequent but laboratory confirmed infection is not necessarily associated with infant abnormalities.

Highlights of the 12th International Bordetella Symposium.

To commemorate the 100th anniversary of the Nobel prize being awarded to Jules Bordet, the discoverer of Bordetella pertussis, the 12th International Bordetella Symposium was held from 9 to 12 April 2019 at the Université Libre de Bruxelles, where Jules Bordet studied and was Professor of Microbiology. The symposium attracted more than 300 Bordetella experts from 34 countries. They discussed the latest epidemiologic data and clinical aspects of pertussis, Bordetella biology and pathogenesis, immunology and vaccine development, and genomics and evolution. Advanced technological and methodological tools provided novel insights into the genomic diversity of Bordetella and a better understanding of pertussis disease and vaccine performance. New molecular approaches revealed previously unrecognized complexity of virulence gene regulation. Innovative insights into the immune responses to infection by Bordetella resulted in the development of new vaccine candidates. Such discoveries will aid in the design of more effective approaches to control pertussis and other Bordetella-related diseases.

The sociology of the antivaccine movement.

Skepticism and misinformation relating to vaccines is not new. The benefits of all our present routinely used vaccines outweigh any risks. In relatively recent times there has been a 'war on science' and relating to this, is the present antivaccine movement. Today, social media is a major contributor to vaccine misinformation. A recent Gallup poll noted that public support for vaccines today is significantly lower than it was in 2001. Social scientists have presented the problem of the antivaccine movement quite well; but mechanisms for addressing it are far from clear. We suggest that physicians and other health care workers should not use social media for vaccine messages. A long-term approach would be to introduce science/epidemiological education in grade school and high school as well as in college.

The Susceptibility to Other Infectious Diseases Following Measles During a Three Year Observation Period in Switzerland.

BACKGROUND: Measles virus infection leads to significant immunosuppression. In developing countries, this translates to an increased nonspecific mortality, whereas its effects in developed countries are less clear. METHODS: We performed a cohort study to investigate whether children hospitalized with measles (cases) between 2000 and 2015 in Switzerland would have a higher frequency of hospital admissions due to other infectious diseases thereafter than children who did not have measles (controls). Cases were identified by ICD-10 discharge diagnoses for measles and/or keyword search and matched to 2 controls by time of hospitalization, age and sex. All hospitalizations ≤3 years after original admission, infectious or noninfectious in origin, were identified in cases and controls. RESULTS: One hundred thirteen cases (56% males), mean age 9.0 years (range 2 weeks-17.8 years), and 196 controls were identified. Twelve rehospitalizations due to an infectious disease occurred in 11 cases and 6 in 6 controls (episode rates 0.106 versus 0.031 per person; ratio 3.47; 95% CI: 1.20-11.3; P = 0.012) in 3 years of follow-up. Of these, 9 and 3 occurred in cases and controls, respectively, during year 1 [ratio 5.20 (95% CI: 1.30-29.88; P = 0.012)]. Infectious diseases following measles affected various organ systems, were neither particularly severe nor fatal and revealed no specific pattern. CONCLUSIONS: The increased risk for nonspecific infectious disease hospitalizations supports the concept of immunologic amnesia after measles. Universal immunization against measles provides additional benefit beyond protection against measles itself.

Measles antibody levels among vaccinated and unvaccinated children 6-59 months of age in the Democratic Republic of the Congo, 2013-2014.

BACKGROUND: Measles is endemic in the Democratic Republic of the Congo (DRC), and 89-94% herd immunity is required to halt its transmission. Much of the World Health Organization African Region, including the DRC, has vaccination coverage below the 95% level required to eliminate measles, heightening concern of inadequate measles immunity. METHODS: We assessed 6706 children aged 6-59 months whose mothers were selected for interview in the 2013-2014 DRC Demographic and Health Survey. History of measles was obtained by maternal report, and classification of children who had measles was completed using maternal recall and measles immunoglobulin G serostatus obtained from a multiplex chemiluminescent automated immunoassay dried blood spot analysis. A logistic regression model was used to identify associations of covariates with measles and seroprotection, and vaccine effectiveness (VE) was calculated. RESULTS: Out of our sample, 64% of children were seroprotected. Measles vaccination was associated with protection against measles (OR: 0.15, 95% CI: 0.03, 0.81) when administered to children 12 months of age or older. Vaccination was predictive of seroprotection at all ages. VE was highest (88%) among children 12-24 months of age. CONCLUSION: Our results demonstrated lower than expected seroprotection against measles among vaccinated children. Understanding the factors that affect host immunity to measles will aid in developing more efficient and effective immunization programs in DRC.

Early Clinical Infancy Outcomes for Microcephaly and/or Small for Gestational Age Zika-Exposed Infants.

BACKGROUND: Zika-exposed infants with microcephaly (proportional or disproportional) and those who are small for gestational age without microcephaly should be closely followed, particularly their growth trajectories. They are at high risk of adverse outcomes in the first year of life.Antenatal Zika virus (ZIKV) exposure may lead to adverse infant outcomes including microcephaly and being small for gestational age (SGA). ZIKV-exposed infants with a diagnosis of microcephaly (proportional [PM] or disproportional [DM]) or SGA at birth were evaluated with anthropometric measurements and health outcomes. METHODS: Infants had laboratory-confirmed ZIKV exposure in Brazil. PM, DM, or SGA classification was based on head circumference and weight. First-year growth parameters and clinical outcomes were recorded with analyses performed. RESULTS: Among the 156 ZIKV-exposed infants, 14 (9.0%) were SGA, 13 (8.3%) PM, 13 (8.3%) DM, and 116 (74.4%) were neither SGA nor had microcephaly (NSNM). High rates of any neurologic, ophthalmologic, and hearing abnormalities were observed for PM (100%), DM (100%), and SGA (42.9%) vs NSNM infants (18.3%; P <.001); odds ratio [OR], 3.4 (95% confidence interval [CI], 1.1-10.7) for SGA vs NSNM. Neuroimaging abnormalities were seen in 100% of PM and DM and in 42.9% of SGA vs NSNM infants 16%; (P <.001); OR 3.9 (95% CI, 1.2-12.8) for SGA vs NSNM. Growth rates by z score, particularly for microcephaly infants, were poor after birth but showed improvement beyond 4 months of life. CONCLUSIONS: ZIKV-exposed infants with microcephaly (PM and DM) had similarly high rates of adverse outcomes but showed improvement in growth measurements beyond 4 months of life. While SGA infants had fewer adverse outcomes compared with microcephaly infants, notable adverse outcomes were observed in some; their odds of having adverse outcomes were 3 to 4 times greater compared to NSNM infants.Zika-exposed infants with microcephaly, irrespective of being proportional or disproportional, and those who are small for gestational age without microcephaly should be closely followed, particularly their growth trajectories. They are at high risk of adverse outcomes in the first year of life.

Sex differences in main olfactory system pathways involved in psychosexual function.

We summarize literature from animal and human studies assessing sex differences in the ability of the main olfactory system to detect and process sex-specific olfactory signals ("pheromones") that control the expression of psychosexual functions in males and females. A case is made in non primate mammals for an obligatory role of pheromonal signaling via the main olfactory system (in addition to the vomeronasal-accessory olfactory system) in mate recognition and sexual arousal, with male-specific as well as female-specific pheromones subserving these functions in the opposite sex. Although the case for an obligatory role of pheromones in mate recognition and mating among old world primates, including humans, is weaker, we review the current literature assessing the role of putative human pheromones (eg, AND, EST, "copulin"), detected by the main olfactory system, in promoting mate choice and mating in men and women. Based on animal studies, we hypothesize that sexually dimorphic effects of putative human pheromones are mediated via main olfactory inputs to the medial amygdala which, in turn, transmits olfactory information to sites in the hypothalamus that regulate reproduction.

Delayed childhood neurodevelopment and neurosensory alterations in the second year of life in a prospective cohort of ZIKV-exposed children.

We report neurodevelopmental outcomes in 216 infants followed since the time of PCR-confirmed maternal Zika virus (ZIKV) infection in pregnancy during the Rio de Janeiro epidemic of 2015-2016 (refs. 1,2). Neurodevelopment was assessed by Bayley Scales of Infant and Toddler Development, third edition (Bayley-III; cognitive, language and motor domains) in 146 children and through neurodevelopment questionnaires/neurological examinations in 70 remaining children. Complete eye exams (n = 137) and hearing assessments (n = 114) were also performed. Below-average neurodevelopment and/or abnormal eye or hearing assessments were noted in 31.5% of children between 7 and 32 months of age. Among children assessed by Bayley-III, 12% scored below -2 s.d. (score <70; a score of 100 ± 2 s.d. is the range) in at least one domain; and 28% scored between -1 and -2 s.d. in any domain (scores <85-70). Language function was most affected, with 35% of 146 children below average. Improved neurodevelopmental outcomes were noted in female children, term babies, children with normal eye exams and maternal infection later in pregnancy (P = 0.01). We noted resolution of microcephaly with normal neurodevelopment in two of eight children, development of secondary microcephaly in two other children and autism spectrum disorder in three previously healthy children in the second year of life.