The immune status of migrant populations in Europe and implications for vaccine-preventable disease control: a systematic review and meta-analysis.

BACKGROUND: Ensuring vaccination coverage reaches established herd immunity thresholds (HIT) is the cornerstone of any vaccination programme. Diverse migrant populations in European countries have been associated with cases of vaccine-preventable diseases (VPD) and outbreaks, yet it is not clear to what extent they are an under-immunised group. METHODS: We did a systematic review and meta-analysis to synthesise peer-reviewed published primary research reporting data on the immune status of migrants in EU/EEA countries, the UK and Switzerland, calculating their pooled immunity coverage for measles, mumps, rubella, and diphtheria using random-effects models. We searched on Web of Science, Embase, Global Health and MEDLINE (January 1st 2000 to June 10th 2022), with no language restrictions. The protocol is registered with PROSPERO (CRD42018103666). FINDINGS: Of 1103 abstracts screened, 62 met eligibility criteria, of which 39 were included in the meta-analysis. The meta-analysis included 75 089 migrants, predominantly from outside Europe. Pooled immunity coverage among migrant populations was well below the recommended HIT for diphtheria (n = 7, 57.4% [95% CI: 43.1-71.7%] I2 = 99% vs HIT 83-86%), measles (n = 21, 83.7% [95% CI: 79.2-88.2] I2 = 99% vs HIT 93-95%), and mumps (n = 8, 67.1% [95% CI: 50.6-83.6] I2 = 99% vs HIT 88-93%), and midway for rubella (n = 29, 85.6% [95% CI: 83.1-88.1%] I2 = 99% vs HIT 83-94%), with high heterogeneity across studies. INTERPRETATION: Migrants in Europe are an under-immunised group for a range of important VPDs, with this study reinforcing the importance of engaging children, adolescents, and adults in 'catch-up' vaccination initiatives on arrival for vaccines, doses, and boosters they may have missed in their home countries. Co-designing strategies to strengthen catch-up vaccination across the life-course in under-immunised groups is an important next step if we are to meet European and global targets for VPD elimination and control and ensure vaccine equity.

Co-circulation of Chikungunya Virus during the 2015-2017 Zika Virus Outbreak in Pernambuco, Brazil: An Analysis of the Microcephaly Epidemic Research Group Pregnancy Cohort.

Co-circulation of arthropod-borne viruses, particularly those with shared mosquito vectors like Zika (ZIKV) and Chikungunya (CHIKV), is increasingly reported. An accurate differential diagnosis between ZIKV and CHIKV is of high clinical importance, especially in the context of pregnancy, but remains challenging due to limitations in the availability of specialized laboratory testing facilities. Using data collected from the prospective pregnancy cohort study of the Microcephaly Epidemic Research Group, which followed up pregnant persons with rash during the peak and decline of the 2015-2017 ZIKV epidemic in Recife, Pernambuco, Brazil, this study aims to describe the geographic and temporal distribution of ZIKV and CHIKV infections and to investigate the extent to which ZIKV and CHIKV infections may be clinically differentiable. Between December 2015 and June 2017, we observed evidence of co-circulation with laboratory confirmation of 213 ZIKV mono-infections, 55 CHIKV mono-infections, and 58 sequential ZIKV/CHIKV infections (i.e., cases with evidence of acute ZIKV infection with concomitant serological evidence of recent CHIKV infection). In logistic regressions with adjustment for maternal age, ZIKV mono-infected cases had lower odds than CHIKV mono-infected cases of presenting with arthralgia (aOR, 99% CI: 0.33, 0.15-0.74), arthritis (0.35, 0.14-0.85), fatigue (0.40, 0.17-0.96), and headache (0.44, 0.19-1.90). However, sequential ZIKV/CHIKV infections complicated discrimination, as they did not significantly differ in clinical presentation from CHIKV mono-infections. These findings suggest clinical symptoms alone may be insufficient for differentiating between ZIKV and CHIKV infections during pregnancy and therefore laboratory diagnostics continue to be a valuable tool for tailoring care in the event of arboviral co-circulation.

Three-Year Clinical Follow-Up of Children Intrauterine Exposed to Zika Virus.

Congenital Zika virus (ZIKV) infection may present with a broad spectrum of clinical manifestations. Some sequelae, particularly neurodevelopmental problems, may have a later onset. We conducted a prospective cohort study of 799 high-risk pregnant women who were followed up until delivery. Eighty-three women and/or newborns were considered ZIKV exposed and/or infected. Laboratory diagnosis was made by polymerase chain reaction in the pregnant mothers and their respective newborns, as well as Dengue virus, Chikungunya virus, and ZIKV serology. Serology for toxoplasmosis, rubella, cytomegalovirus, herpes simplex virus, and syphilis infections were also performed in microcephalic newborns. The newborns included in the study were followed up until their third birthday. Developmental delay was observed in nine patients (13.2%): mild cognitive delay in three patients, speech delay in three patients, autism spectrum disorder in two patients, and severe neurological abnormalities in one microcephalic patient; sensorineural hearing loss, three patients and dysphagia, six patients. Microcephaly due to ZIKV occurred in three patients (3.6%). Clinical manifestations can appear after the first year of life in children infected/exposed to ZIKV, emphasizing the need for long-term follow-up.

Postnatal symptomatic Zika virus infections in children and adolescents: A systematic review.

BACKGROUND: Recent Zika virus (ZIKV) outbreaks in the Pacific and the Americas have highlighted clinically significant congenital neurological abnormalities resulting from ZIKV infection in pregnancy. However, little is known about ZIKV infections in children and adolescents, a group that is potentially vulnerable to ZIKV neurovirulence. METHODS: We conducted a systematic review on the clinical presentation and complications of children and adolescents aged 0 to 18 years with a robust diagnosis of ZIKV infection. We searched PubMed, Web of Science, LILACs, and EMBASE until 13 February 2020 and screened reference lists of eligible articles. We assessed the studies' risk of bias using pre-specified criteria. FINDINGS: Our review collated the evidence from 2543 pediatric ZIKV cases representing 17 countries and territories, identified in 1 cohort study, 9 case series and 22 case reports. The most commonly observed signs and symptoms of ZIKV infection in children and adolescents were mild and included fever, rash, conjunctivitis and arthralgia. The frequency of neurological complications was reported only in the largest case series (identified in 1.0% of cases) and in an additional 14 children identified from hospital-based surveillance studies and case reports. ZIKV-related mortality was primarily accompanied by co-morbidity and was reported in one case series (<0.5% of cases) and three case reports. One death was attributed to complications of Guillain-Barré Syndrome secondary to ZIKV infection. CONCLUSIONS AND RELEVANCE: Based on the current evidence, the clinical presentation of ZIKV infection in children and adolescents appears to be primarily mild and similar to the presentation in adults, with rare instances of severe complications and/or mortality. However, reliable estimation of the risks of ZIKV complications in these age groups is limited by the scarcity and quality of published data. Additional prospective studies are needed to improve understanding of the relative frequency of the signs, symptoms, and complications associated with pediatric ZIKV infections and to investigate any potential effects of early life ZIKV exposure on neurodevelopment.

Zika virus infection in pregnancy and infant growth, body composition in the first three months of life: a cohort study.

The implications of Zika Virus exposure in pregnancy for early infant growth remains poorly described. The main goal of this study is to compare the growth, body composition, and feeding modality of infants in the first three months of life by prenatal Zika Virus exposure status. We selected an analytical cohort of 115 infants born without microcephaly, comprising 56 infants with qRT-PCR confirmed exposure to ZIKV during gestation and 59 infants born to women with presumptively no evidence of ZIKV in pregnancy. Infants were evaluated at birth, 1 and 3 months of age in terms of anthropometrics, body composition All the results were adjusted by maternal age, maternal BMI and gestational age. We observe no differences between anthropometric measurements at birth. Mothers in exposed group showed higher BMI. At 1 month and 3 months of age there were differences in mid arm circumference, arm muscle circumference and fat free mass. Weight and length was less in the ZIKV exposed in pregnancy infants and statistically different at 3 month of age. The findings of this investigation provide new evidence that ZIKV exposure in pregnancy may be associated with differences in body composition.

Zika virus infection in pregnancy and its fetomaternal repercussions findings from a prospective cohort study in São Paulo, Brazil / Infecção vertical pelo vírus Zika e suas repercussões feto-maternais: achados de uma coorte de gestantes em Jundiaí, São Paulo

Prior to its arrival in The Americas in 2014, Zika Virus was thought to cause only mild disease. Following the outbreak in Brazil and the declaration of a Public Health Emergency of International Concern by WHO in February 2016, epidemiological and biological evidence has been published which supports a causal link between prenatal Zika Virus (ZIKV) infection and congenital brain abnormalities including microcephaly. This doctoral thesis uses data from The Jundiaí Zika Cohort, a prospective pregnancy and birth cohort which was set up in The State of São Paulo in 2016 to investigate this causal hypothesis further. A total of 748 pregnant women were recruited from the high-risk pregnancy clinic at Jundiaí University Hospital in the period March 2016 to August 2017. Baseline sociodemographic and medical data were collected at recruitment. Biological samples (blood, saliva, urine) were collected from women at enrolment and regular intervals throughout pregnancy. Women were asked to report any symptoms consistent with ZIKV infection (as per the WHO clinical case definition) and to attend the hospital to be assessed clinically and for samples to be taken. Further biological specimens (colostrum, umbilical cord, placenta, neonatal blood, saliva, urine and cerebro-spinal fluid when appropriate) were obtained at delivery. Urine samples were processed for ZIKV RT-PCR and the rest of the biological material has been stored in a secure biorepository. Anthropometric measures were obtained from the neonates at birth. After creating the master database and carrying out the first thorough analysis of the dataset, I created a cohort profile manuscript which thoroughly detailed the creation, the specific methodology and the preliminary findings of The Jundiaí Zika Cohort. I then employed a prospective cohort study design to investigate the extent to which specific symptoms can be utilized to differentiate ZIKV-infected pregnant women from those with other pregnancy-related problems. Finally, I compared the prevalence of adverse fetal outcomes (prematurity, low birth weight, small-forgestational- age, fetal death and microcephaly) by prenatal Zika Virus (ZIKV) exposure status. The main findings are that most pregnant women positive for ZIKV in urine are asymptomatic and do not deliver a baby with microcephaly, that physical symptoms alone do not differentiate between high risk pregnant women positive or negative for ZIKV and that current clinical case definitions have a low sensitivity for detecting ZIKVpositive women living in active ZIKV transmission areas. In addition, ZIKV infection in high risk pregnant women substantially increases the risk of disproportionate microcephaly but not other adverse fetal outcomes. As a result of this research, we propose clinical case definitions for use in pregnant women living in areas with active ZIKV transmission be revised and that disproportion between head circumference and weight during fetal development should