Hepatitis B infection and immunity in migrant children and pregnant persons in Europe: a systematic review and meta-analysis.

BACKGROUND: The WHO's global hepatitis strategy aims to achieve viral hepatitis elimination by 2030. Migrant children and pregnant persons represent an important target group for prevention strategies. However, evidence on the burden of chronic hepatitis B (CHB) infection and the factors affecting its incidence is lacking. METHODS: EMBASE, Global Health, Global Index Medicus, Web of Science and Medline were searched for articles in any language from 1 January 2012 to 8 June 2022. Studies reporting CHB prevalence, disease severity, complications and/or prevention strategies, including vaccination, prevention of vertical transmission and access to care/treatment for migrant children and pregnant migrants, were included. Pooled estimates of CHB prevalence and hepatitis B vaccination (HBV) coverage among migrant children were calculated using random effects meta-analysis. FINDINGS: 42 studies were included, 27 relating to migrant children and 15 to pregnant migrants across 12 European countries, involving data from 64 773 migrants. Migrants had a higher incidence of CHB than host populations. Among children, the pooled prevalence of CHB was higher for unaccompanied minors (UAM) (5%, [95% CI: 3-7%]) compared to other child migrants, including internationally adopted children (IAC) and refugees (1%, [95% CI: 1-2%]). Region of origin was identified as a risk factor for CHB, with children from Africa and pregnant migrants from Africa, Eastern Europe and China at the highest risk. Pooled estimates of HBV vaccine coverage were lower among UAM (12%, [95% CI: 3-21%]) compared to other child migrants (50%, [95% CI: 37-63%]). CONCLUSION: A range of modifiable determinants of HBV prevalence in migrant children and pregnant persons were identified, including sub-optimal screening, prevention and continuum of care. There is a need to develop evidence-based approaches in hepatitis care for these groups, thereby contributing towards global viral hepatitis elimination goals.

A nationwide longitudinal investigation on the role of prenatal exposure to infectious diseases on the onset of chronic conditions in children and adolescents in Brazil.

Background: In utero exposure to infections might set the stage for a chain of events leading to a wide spectrum of long-term health outcomes observed in children and adolescents. This proposal aims to investigate whether syphilis, zika, dengue and chikungunya during pregnancy can increase the risk of the offspring developing a non-infectious chronic condition during childhood and adolescence. Objectives: 1) Estimate the risk of non-infectious chronic conditions associated to syphilis, zika, dengue and chikungunya during pregnancy and when appropriate, explore if the risk varies by timing during pregnancy when the infection is acquired (first, second or third trimester) and severity (such as severe or mild dengue); 2) Investigate whether in uterus exposure to maternal infection affects the growth pattern of children and adolescents; 3) Examine the extent to which the relationship between maternal infection and non-infectious chronic outcomes are mediated by intrauterine growth restriction and preterm birth. Methods: We will compare health outcomes and growth trajectories of children and adolescents born to mothers with and without specific infections during pregnancy using conventional multivariable regression in the whole study population, in a within sibship design, using the subgroup of offspring with at least one sibling who is not exposed to the infection, and negative control outcome. Then we will decompose the direct and mediated effects (by preterm birth and small for gestational age) of maternal infection on chronic disorders. Results and Conclusions: The results from this study will advance our understanding of the relationship between infections during pregnancy and chronic disorders, with widespread implications enabling targeting of critical points along the path from in utero exposure to outcomes to avoid or mitigate illness and disability over the life course.

It is not clear whether when moms get an infection during pregnancy, it might affect their child's long-term health. This means that we do not know whether we could prevent some chronic conditions by screening for and treating infections during pregnancy or by monitoring and treating the child after their birth. In this study, we are going to look at whether infections affecting low­and middle-income countries, like syphilis, neglected tropical diseases such as dengue, zika, and chikungunya, might make children more likely to develop cancer, neurological problems, autoimmune diseases, or obesity when they grow up. We will also check if these risks are connected to things like being born too soon or small. We will use a unique data set from Brazil that follows people from birth (the CIDACS birth cohort). We'll compare the health and growth of children from infancy to teenage years whose mothers had certain infections during pregnancy with those whose mothers did not. The findings from this study will help us learn more about how infections during pregnancy impact the health of children. This knowledge could help us find ways to prevent or lessen the effect of illness and disability throughout a person's life, starting from before they are even born.

Paediatric, maternal, and congenital mpox: a systematic review and meta-analysis.

BACKGROUND: Although mpox has been detected in paediatric populations in central and west Africa for decades, evidence synthesis on paediatric, maternal, and congenital mpox, and the use of vaccines and therapeutics in these groups, is lacking. A systematic review is therefore indicated to set the research agenda. METHODS: We conducted a systematic review and meta-analysis, searching articles in Embase, Global Health, MEDLINE, CINAHL, Web of Science, Scopus, SciELO, and WHO databases from inception to April 17, 2023. We included studies reporting primary data on at least one case of confirmed, suspected, or probable paediatric, maternal, or congenital mpox in humans or the use of third-generation smallpox or mpox vaccines, targeted antivirals, or immune therapies in at least one case in our population of interest. We included clinical trials and observational studies in humans and excluded reviews, commentaries, and grey literature. A pooled estimate of the paediatric case fatality ratio was obtained using random-effects meta-analysis. This study is registered with PROSPERO (CRD420223336648). FINDINGS: Of the 61 studies, 53 reported paediatric outcomes (n=2123 cases), seven reported maternal or congenital outcomes (n=32 cases), two reported vaccine safety (n=28 recipients), and three reported transmission during breastfeeding (n=4 cases). While a subset of seven observational studies (21 children and 12 pregnant individuals) reported uneventful treatment with tecovirimat, there were no randomised trials reporting safety or efficacy for any therapeutic agent. Among children, the commonest clinical features included rash (86 [100%] of 86), fever (63 [73%] of 86), and lymphadenopathy (40 [47%] of 86). Among pregnant individuals, rash was reported in 23 (100%) of 23; fever and lymphadenopathy were less common (six [26%] and three [13%] of 23, respectively). Most paediatric complications (12 [60%] of 20) arose from secondary bacterial infections. The pooled paediatric case fatality ratio was 11% (95% CI 4-20), I2=75%. Data from 12 pregnancies showed half resulted in fetal death. Research on vaccine and immune globulin safety remains scarce for children and absent for pregnant individuals. INTERPRETATION: Our review highlights critical knowledge gaps in the epidemiology, prevention, and treatment of mpox in children and pregnant individuals, especially those residing in endemic countries. Increased funding, international collaboration, and equitable research is needed to inform mpox control strategies tailored for at-risk communities in endemic countries. FUNDING: None. TRANSLATIONS: For the French, Spanish and Portuguese translations of the abstract see Supplementary Materials section.

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 (HITs) is the cornerstone of any vaccination programme. Diverse migrant populations in European countries have been associated with cases of vaccine-preventable diseases (VPDs) and outbreaks, yet it is not clear to what extent they are an under-immunized group. METHODS: We did a systematic review and meta-analysis to synthesize 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 (1 January 2000 to 10 June 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% confidence interval (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-immunized 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-immunized groups is an important next step if we are to meet European and global targets for VPD elimination and control and ensure vaccine equity.

Prenatal exposure to ambient air pollution and subsequent risk of lower respiratory tract infections in childhood and adolescence: A systematic review.

BACKGROUND: Pregnancy represents a critical window of vulnerability to the harmful effects of air pollution on health. However, long-term consequences such as risk of having lower respiratory tract infections (LRTIs) are less explored. This systematic review aims to synthesize previous research on prenatal exposure to ambient (outdoor) air pollution and LRTIs in childhood and adolescence. METHODS: We systematically searched Embase, MEDLINE, Web of Science Core Collection, CINAHL, and Global Health up to May 17, 2024. We included peer-reviewed publications of studies which investigated the association between prenatal exposure to ambient air pollution and LRTIs up to the age of 19. We excluded conference abstracts, study protocols, review articles, and grey literature. Screening and data extraction was conducted by two reviewers independently. We used the Office of Health Assessment and Translation tool to assess risk of bias and conducted a narrative synthesis. RESULTS: The search yielded 6056 records, of which 16 publications describing 12 research studies were eligible for the synthesis. All studies were conducted in high- or upper-middle-income countries in Europe or Asia. Half (6) of the studies focused on LRTIs occurring within the first three years of life, and the others also included LRTIs in older children (up to age 14). Air pollutants investigated included nitrogen dioxide, sulphur dioxide, particulate matter (PM2.5: diameter ≤2.5 µm and PM10: diameter ≤10 µm), carbon monoxide, ozone, and benzene. Findings on a potential association between prenatal ambient air pollution exposure and LRTIs were inconclusive, without a clear and consistent direction. There was some suggestion of a positive association with prenatal PM2.5 exposure. The small number of studies identified, their poor geographical representation, and their methodological limitations including concerns for risk of bias preclude more definitive conclusions. CONCLUSION: The available published evidence is insufficient to establish whether prenatal exposure to ambient air pollution increases risk of LRTIs in children and adolescents. With many populations exposed to high levels of air pollution, there is an urgent need for research in more diverse settings, more transparent reporting of methods, and exploring how, when, and for whom prenatal exposure to ambient air pollution leads to the greatest health risks. PROSPERO REGISTRATION NUMBER: CRD42023407689.

Perinatal health outcomes of international migrant women in Brazil: A nationwide data linkage study of the CIDACS birth cohort (2011-2018).

BACKGROUND: We investigated perinatal outcomes among live births from international migrant and local-born mothers in a cohort of low-income individuals in Brazil. METHODS: We linked nationwide birth registries to mortality records and socioeconomic data from the CIDACS Birth Cohort and studied singleton live births of women aged 10-49 years from 1st January 2011 to 31st December 2018. We used logistic regressions to investigate differences in antenatal care, adverse pregnancy outcomes, and neonatal (i.e., ≤28 days) mortality among international migrants compared to non-migrants in Brazil; and explored the interaction between migration, race/ethnicity and living in international border municipalities. RESULTS: We studied 10,279,011 live births, of which 9469 (0.1 %) were born to international migrants. Migrant women were more likely than their Brazilian-born counterparts to have a previous foetal loss (ORadj: 1.16, 1.11-1.22), a delayed start of antenatal care (i.e., beyond 1st trimester) (1.22, 95%CI:1.16-1.28), a newborn who is large for gestational age (1.29, 1.22-1.36), or a newborn with congenital anomalies (1.37, 1.14-1.65). Conversely, migrant women were less likely to deliver prematurely (0.89, 0.82-0.95) or have a low birth weight infant (0.74, 0.68-0.81). There were no differences in neonatal mortality rates between migrants and non-migrants. Our analyses also showed that, when disparities in perinatal outcomes were present, disparities were mostly concentrated among indigenous mothers in international borders and among live births of Black mothers in non-borders. CONCLUSION: Although live births of international migrants generally have lower rates of adverse birth outcomes, our results suggest that indigenous and Black migrant mothers may face disproportionate barriers to accessing antenatal care.

Understanding the views of adult migrants around catch-up vaccination for missed routine immunisations to define strategies to improve coverage: A UK in-depth interview study.

BACKGROUND: The World Health Organization's (WHO) Immunization Agenda 2030 emphasises ensuring equitable access to vaccination across the life course. This includes placing an emphasis on migrant populations who may have missed key childhood vaccines, doses, and boosters due to disrupted healthcare systems and the migration process, or differing vaccination schedules in home countries. Guidelines exist in the UK for offering catch-up vaccinations to adolscent and adult migrants with incomplete or uncertain vaccination status (including MMR, Td-IPV, MenACWY, HPV), but emerging evidence suggests awareness and implementation in primary care is poor. It is unclear whether patient-level barriers to uptake of catch-up vaccinations also exist. We explored experiences and views around catch-up vaccination among adult migrants from a range of backgrounds, to define strategies for improving catch-up vaccination policy and practice. METHODS: In-depth semi-structured interviews were carried out in two phases with adult migrant populations (refugees, asylum seekers, undocumented migrants, those with no recourse to public funds) on views and experiences around vaccination, involving a team of peer researchers from specific migrant communities trained through the study. In Phase 1, we conducted remote interviews with migrants resident in the UK for < 10 years, from diverse backgrounds. In Phase 2, we engaged specifically Congolese and Angolan migrants as part of a community-based participatory study. Topic guides were developed iteratively and piloted. Participants were recruited using purposive, opportunistic and snowball sampling methods. Interviews were conducted in English (interpreters offered), Lingala or French and were audio-recorded, transcribed and analysed using a thematic framework approach in NVivo 12. RESULTS: 71 participants (39 in Phase 1, 32 in Phase 2) were interviewed (Mean age 43.6 [SD:12.4] years, 69% female, mean 9.5 [SD:7] years in the UK). Aside from COVID-19 vaccines, most participants reported never having been offered vaccinations or asked about their vaccination history since arriving in the UK as adults. Few participants mentioned being offered specific catch-up vaccines (e.g. MMR/Td-IPV) when attending a healthcare facility on arrival in the UK. Vaccines such as flu vaccines, pregnancy-related or pre-travel vaccination were more commonly mentioned. In general, participants were not aware of adult catch-up vaccination but regarded it positively when it was explained. A few participants expressed concerns about side-effects, risks/inconveniences associated with access (e.g. links to immigration authorities, travel costs), preference for natural remedies, and hesitancy to engage in further vaccination campaigns due to the intensity of COVID-19 vaccination campaigns. Trust was a major factor in vaccination decisions, with distinctions noted within and between groups; some held a healthcare professional's recommendation in high regard, while others were less trusting towards the healthcare system because of negative experiences of the NHS and past experiences of discrimination, injustice and marginalisation by wider authorities. CONCLUSIONS: The major barrier to adult catch-up vaccination for missed routine immunisations and doses in migrant communities in the UK is the limited opportunities, recommendations or tailored vaccination information presented to migrants by health services. This could be improved with financial incentives for provision of catch-up vaccination in UK primary care, alongside training of healthcare professionals to support catch-up immunisation and raise awareness of existing guidelines. It will also be essential to address root causes of mistrust around vaccination, where it exists among migrants, by working closely with communities to understand their needs and meaningfully involving migrant populations in co-producing tailored information campaigns and culturally relevant interventions to improve coverage.

Strengthening life-course immunisation in migrant populations: access, equity, and inclusion.

Adult and adolescent migrants worldwide, and those arriving in Europe, are an under-immunised group for routine vaccinations due to missed childhood vaccines and doses in their countries of origin, and their subsequent marginalisation from health and vaccination systems. Declining population-level coverage for routine vaccines across Europe, which has accelerated post-pandemic, places these and other under-immunised populations at even greater risk of vaccine-preventable diseases. However, despite clear guidelines around the importance of delivering 'catch-up' vaccination throughout the life-course, migrants are rarely effectively incorporated into routine vaccination programmes on arrival to Europe. These populations have subsequently been involved in outbreaks, including measles and diphtheria, and are missing opportunities to receive more recently introduced vaccines such as HPV to align them with European vaccine schedules. WHO's new Immunization Agenda 2030 places a renewed emphasis on equitable access to vaccine systems and integrating catch-up vaccination for missed vaccines and doses throughout the life-course. In addition, lessons learned and innovations from the COVID-19 pandemic merit further consideration in the design and delivery of more inclusive vaccination programmes. We describe current gaps in policy and practice around life-course vaccination in migrant populations, key factors that drive low vaccine uptake and coverage, and explore the benefits of participatory approaches to designing and delivering interventions with impacted communities, to define new strategies to advance vaccine equity across the Region.

Beyond arrival: safeguarding unaccompanied asylum-seeking children in the UK.

Unaccompanied children (also called unaccompanied minors) are children who have been separated from both parents and other relatives and are not being cared for by an adult who, by law or custom, is responsible for doing so. From 2010 to 2020, unaccompanied minors accounted on average for 15.4% of the total number of first-time asylum applicants aged less than 18 years in the UK. These young people risk their lives and undergo traumatic journeys in search of a better life. However, when they arrive in the UK, they are vulnerable to significant ongoing traumatic experiences.In this review, we look at the reasons young people are forced to flee their countries, how they make their journey, and the risks and dangers they face along the way. We examine safety and victimisation risks faced by children and young people after arrival in the UK, which mechanisms and processes exist to safeguard these individuals, and examine the data available on outcomes of unaccompanied asylum-seeking child (UASC. Finally, we share two case examples that represent both the strengths and weaknesses of existing processes for UASC.

Frailty in hemodialysis patients: results of a screening program and multidisciplinary interventions.

Background: The number of frail patients of advanced age with end-stage kidney disease (ESKD) undergoing hemodialysis is increasing globally. Here we evaluated a frailty screening program of ESKD patients starting hemodialysis, and subsequent multidisciplinary interventions. Methods: This was a prospective observational study of ESKD patients in a hemodialysis program. Patients were evaluated for frailty (Fried frail phenotype) before and after a 12-month period. Patients followed standard clinical practice at our hospital, which included assessment and multidisciplinary interventions for nutritional (malnutrition-inflammation score, protein-energy wasting), physical [short physical performance battery (SPPB)] and psychological status. Results: A total of 167 patients (mean ± standard deviation age 67.8 ± 15.4 years) were screened for frailty, and 108 completed the program. At screening, 27.9% of the patients were frail, 40.0% pre-frail and 32.1% non-frail. Nutritional interventions (enrichment, oral nutritional supplements, intradialytic parenteral nutrition) resulted in stable nutritional status for most frail and pre-frail patients after 12 months. Patients following recommendations for intradialytic, home-based or combined physical exercise presented improved or stable in SPPB scores after 12 months, compared with those that did not follow recommendations, especially in the frail and pre-frail population (P = .025). A rate of 0.05 falls/patient/year was observed. More than 60% of frail patients presented high scores of sadness and anxiety. Conclusions: Frailty screening, together with coordinated interventions by nutritionists, physiotherapists, psychologists and nurses, preserved the health status of ESKD patients starting hemodialysis. Frailty assessment helped in advising patients on individual nutritional, physical or psychological needs.

Case Report: A Severe Paediatric Presentation of COVID-19 in APDS2 Immunodeficiency.

Critical respiratory manifestations of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) are rare in children, and little is known about how immunocompromised children respond to the infection. We report a case of a 4-year-old boy with activated PI3K delta syndrome type 2 (APDS2) with a protracted and severe COVID-19 course with both inflammatory and acute respiratory features. He was treated with remdesivir, nitazoxanide, high-dose corticosteroids, and tocilizumab and made a full recovery. We propose that remdesivir may be used in combination with nitazoxanide to improve viral clearance and reduce the chance of resistance in treating acute SARS-CoV-2 infection.

A Whole-child, whole-family approach to health assessments for asylum-seeking children.

In 2020, 21% of people who sought asylum in the UK were children. This population has complex interconnecting health and social needs. Assessment requires a holistic approach, with consideration of physical and mental health in addition to social and developmental well-being, within the whole family group. A trauma-informed life-cycle and intergenerational care approach is important. This article, aimed at all health professionals who may work with asylum-seeking families, outlines the best practice principles for undertaking health assessments in migrant children and young people.

Socioeconomic risk markers of arthropod-borne virus (arbovirus) infections: a systematic literature review and meta-analysis.

INTRODUCTION: Arthropod-borne viruses (arboviruses) are of notable public health importance worldwide, owing to their potential to cause explosive outbreaks and induce debilitating and potentially life-threatening disease manifestations. This systematic review and meta-analysis aims to assess the relationship between markers of socioeconomic position (SEP) and infection due to arboviruses with mosquito vectors. METHODS: We conducted a systematic search on PubMed, Embase, and LILACS databases to identify studies published between 1980 and 2020 that measured the association of SEP markers with arbovirus infection. We included observational studies without geographic location or age restrictions. We excluded studies from grey literature, reviews and ecological studies. Study findings were extracted and summarised, and pooled estimates were obtained using random-effects meta-analyses. RESULTS: We identified 36 observational studies using data pertaining to 106 524 study participants in 23 geographic locations that empirically examined the relationship between socioeconomic factors and infections caused by seven arboviruses (dengue, chikungunya, Japanese encephalitis, Rift Valley fever, Sindbis, West Nile and Zika viruses). While results were varied, descriptive synthesis pointed to a higher risk of arbovirus infection associated with markers of lower SEP, including lower education, income poverty, low healthcare coverage, poor housing materials, interrupted water supply, marital status (married, divorced or widowed), non-white ethnicities and migration status. Pooled crude estimates indicated an increased risk of arboviral infection associated with lower education (risk ratio, RR 1.5 95% CI 1.3 to 1.9); I2=83.1%), interruption of water supply (RR 1.2; 95% CI 1.1 to 1.3; I2=0.0%) and having been married (RR 1.5 95% CI 1.1 to 2.1; I2=85.2%). CONCLUSION: Evidence from this systematic review suggests that lower SEP increases the risk of acquiring arboviral infection; however, there was large heterogeneity across studies. Further studies are required to delineate the relationship between specific individual, household and community-level SEP indicators and arbovirus infection risks to help inform targeted public health interventions. PROSPERO REGISTRATION NUMBER: CRD42019158572.

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.

Epidemic preparedness: Prenatal Zika virus screening during the next epidemic.

Zika virus (ZIKV) is a vectorborne infectious agent of global public health significance due to its potential to cause severe teratogenic outcomes. The question of whether health systems should consider adopting screening programmes for ZIKV infections during pregnancy warrants consideration. In this analysis, we apply the Wilson-Jungner framework to appraise the potential utility of a prenatal ZIKV screening programme, outline potential screening strategies within the case-finding pathway, and consider other epidemiological factors that may influence the planning of such a screening programme. Our evaluation of a potential prenatal ZIKV screening programme highlights factors affirming its usefulness, including the importance of Congenital Zika Syndrome as a public health problem and the existence of analogous congenital prenatal screening programmes for STORCH agents (syphilis, toxoplasmosis, others (eg, human immunodeficiency virus, varicella-zoster virus, parvovirus B19), rubella, cytomegalovirus, and herpes simplex virus). However, our assessment also reveals key barriers to implementation, such as the need for more accurate diagnostic tests, effective antiviral treatments, increased social service capacity, and surveillance. Given that the reemergence of ZIKV is likely, we provide a guiding framework for policymakers and public health leaders that can be further elaborated and adapted to different contexts in order to reduce the burden of adverse ZIKV-related birth outcomes during future outbreaks.

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.

The Microcephaly Epidemic Research Group Paediatric Cohort (MERG-PC): A Cohort Profile.

This cohort profile aims to describe the ongoing follow-up of children in the Microcephaly Epidemic Research Group Paediatric Cohort (MERG-PC). The profile details the context and aims of the study, study population, methodology including assessments, and key results and publications to date. The children that make up MERG-PC were born in Recife or within 120 km of the city, in Pernambuco/Brazil, the epicentre of the microcephaly epidemic. MERG-PC includes children from four groups recruited at different stages of the ZIKV microcephaly epidemic in Pernambuco, i.e., the Outpatient Group (OG/n = 195), the Microcephaly Case-Control Study (MCCS/n = 80), the MERG Pregnant Women Cohort (MERG-PWC/n = 336), and the Control Group (CG/n = 100). We developed a comprehensive array of clinical, laboratory, and imaging assessments that were undertaken by a 'task force' of clinical specialists in a single day at 3, 6, 12, 18 months of age, and annually from 24 months. Children from MCCS and CG had their baseline assessment at birth and children from the other groups, at the first evaluation by the task force. The baseline cohort includes 711 children born between February 2015 and February 2019. Children's characteristics at baseline, excluding CG, were as follows: 32.6% (184/565) had microcephaly, 47% (263/559) had at least one physical abnormality, 29.5% (160/543) had at least one neurological abnormality, and 46.2% (257/556) had at least one ophthalmological abnormality. This ongoing cohort has contributed to the understanding of the congenital Zika syndrome (CZS) spectrum. The cohort has provided descriptions of paediatric neurodevelopment and early epilepsy, including EEG patterns and treatment response, and information on the frequency and characteristics of oropharyngeal dysphagia; cryptorchidism and its surgical findings; endocrine dysfunction; and adenoid hypertrophy in children with Zika-related microcephaly. The study protocols and questionnaires were shared across Brazilian states to enable harmonization across the different studies investigating microcephaly and CZS, providing the opportunity for the Zika Brazilian Cohorts Consortium to be formed, uniting all the ZIKV clinical cohorts in Brazil.

Can Zika Virus Infection in High Risk Pregnant Women Be Differentiated on the Basis of Symptoms?

Zika virus (ZIKV) infection in pregnancy is associated with congenital neurological abnormalities. Our understanding of the full clinical spectrum of ZIKV infection is incomplete. Using data from this prospective cohort study consisting of 650 women attending a high-risk pregnancy clinic during the Zika virus outbreak in Brazil, we investigated the extent to which specific symptoms can be utilized to differentiate ZIKV-infected pregnant women from those with other pregnancy-related problems. All were tested for ZIKV in urine by RT-qPCR. Demographic and clinical data including physical symptoms during follow-up were recorded and analyzed with respect to Zika virus exposure status. Forty-eight (7.4%) women were positive for ZIKV by RT-qPCR. The majority (70.8%) were asymptomatic, and only four ZIKV-positive women (8.3%) reported symptoms during pregnancy that met the WHO case definition. Zika-positive and -negative women reported similar frequencies of ZIKV-like symptoms (as per the WHO definition): fever (16.7% vs. 13.6%), arthralgia/arthritis (10.4% vs. 11.3%), rash (4.2% vs. 5.3%), and conjunctivitis (2.1% vs. 3.2%). Most pregnant women positive for ZIKV in urine are asymptomatic and do not deliver a baby with microcephaly. Physical symptoms alone did not differentiate between high-risk pregnant women positive or negative for ZIKV.

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 adverse fetal outcomes in São Paulo State, Brazil: a prospective cohort study.

Robust epidemiological and biological evidence supports a causal link between prenatal Zika Virus (ZIKV) infection and congenital brain abnormalities including microcephaly. However, it remains uncertain if ZIKV infection in pregnancy also increases the risk for other adverse fetal and birth outcomes. In a prospective cohort study we investigated the influence of ZIKV on the prevalence of prematurity, low birth weight, small-for-gestational-age, and fetal death as well as microcephaly (i.e., overall and disproportionate) in the offspring of women attending a high-risk pregnancy clinic during the recent ZIKV outbreak in Brazil. During the recruitment period (01 March 2016-23 August 2017), urine samples were tested for ZIKV by RT-PCR from all women attending the high-risk pregnancy clinic at Jundiaí University Hospital and from the neonates after delivery. Of the 574 women evaluated, 44 (7.7%) were ZIKV RT-PCR positive during pregnancy. Of the 409 neonates tested, 19 (4.6%) were ZIKV RT-PCR positive in the first 10 days of life. In this cohort, maternal ZIKV exposure was not associated with increased risks of prematurity, low birth weight, small-for-gestational-age, or fetal death. However, relative to ZIKV-negative neonates, ZIKV-positive infants had a five-fold increased risk of microcephaly overall (RR 5.1, 95% CI 1.2-22.5) and a ten-fold increased risk of disproportionate microcephaly (RR 10.3, 95% CI 2.0-52.6). Our findings provide new evidence that, in a high-risk pregnancy cohort, ZIKV RT-PCR positivity in the neonate at birth is strongly associated with microcephaly. However, ZIKV infection during pregnancy does not appear to influence the risks of prematurity, low birth weight, small-for-gestational-age or fetal death in women who already have gestational comorbidities. The results suggest disproportion between neonatal head circumference and weight may be a useful screening indicator for the detection of congenital microcephaly associated with ZIKV infection.