Developing a novel risk prediction model for severe malarial anemia.

As a pilot study to investigate whether personalized medicine approaches could have value for the reduction of malaria-related mortality in young children, we evaluated questionnaire and biomarker data collected from the Mother Offspring Malaria Study Project birth cohort (Muheza, Tanzania, 2002-2006) at the time of delivery as potential prognostic markers for pediatric severe malarial anemia. Severe malarial anemia, defined here as a Plasmodium falciparum infection accompanied by hemoglobin levels below 50 g/L, is a key manifestation of life-threatening malaria in high transmission regions. For this study sample, a prediction model incorporating cord blood levels of interleukin-1β provided the strongest discrimination of severe malarial anemia risk with a C-index of 0.77 (95% CI 0.70-0.84), whereas a pragmatic model based on sex, gravidity, transmission season at delivery, and bed net possession yielded a more modest C-index of 0.63 (95% CI 0.54-0.71). Although additional studies, ideally incorporating larger sample sizes and higher event per predictor ratios, are needed to externally validate these prediction models, the findings provide proof of concept that risk score-based screening programs could be developed to avert severe malaria cases in early childhood

Mortality among over 6 million internal and international migrants in Brazil: a study using the 100 Million Brazilian Cohort

Background: To understand if migrants living in poverty in low and middle-income countries (LMICs) have mortality advantages over the non-migrant population, we investigated mortality risk patterns among internal and international migrants in Brazil over their life course. / Methods: We linked socio-economic and mortality data from 1st January 2011 to 31st December 2018 in the 100 Million Brazilian Cohort and calculated all-cause and cause-specific age-standardised mortality rates according to individuals' migration status for men and women. Using Cox regression models, we estimated the age- and sex-adjusted mortality hazard ratios (HR) for internal migrants (i.e., Brazilian-born individuals living in a different Brazilian state than their birth) compared to Brazilian-born non-migrants; and for international migrants (i.e., people born in another country) compared to Brazilian-born individuals. / Findings: The study followed up 45,051,476 individuals, of whom 6,057,814 were internal migrants, and 277,230 were international migrants. Internal migrants had similar all-cause mortality compared to Brazilian non-migrants (aHR = 0.99, 95% CI = 0.98–0.99), marginally higher mortality for ischaemic heart diseases (aHR = 1.04, 95% CI = 1.03–1.05) and higher for stroke (aHR = 1.11, 95% CI = 1.09–1.13). Compared to Brazilian-born individuals, international migrants had 18% lower all-cause mortality (aHR = 0.82, 95% CI = 0.80–0.84), with up to 50% lower mortality from interpersonal violence among men (aHR = 0.50, 95% CI = 0.40–0.64), but higher mortality from avoidable causes related to maternal health (aHR = 2.17, 95% CI = 1.17–4.05). / Interpretation: Although internal migrants had similar all-cause mortality, international migrants had lower all-cause mortality compared to non-migrants. Further investigations using intersectional approaches are warranted to understand the marked variations by migration status, age, and sex for specific causes of death, such as elevated maternal mortality and male lower interpersonal violence-related mortality among international migrants

Validating linkage of multiple population-based administrative databases in Brazil

BACKGROUND: Linking routinely-collected data provides an opportunity to measure the effects of exposures that occur before birth on maternal, fetal and infant outcomes. High quality linkage is a prerequisite for producing reliable results, and there are specific challenges in mother-baby linkage. Using population-based administrative databases from Brazil, this study aimed to estimate the accuracy of linkage between maternal deaths and birth outcomes and dengue notifications, and to identify potential sources of bias when assessing the risk of maternal death due to dengue in pregnancy. METHODS: We identified women with dengue during pregnancy in a previously linked dataset of dengue notifications in women who had experienced a live birth or stillbirth during 2007-2012. We then linked this dataset with maternal death records probabilistically using maternal name, age and municipality. We estimated the accuracy of the linkage, and examined the characteristics of false-matches and missed-matches to identify any sources of bias. RESULTS: Of the 10,259 maternal deaths recorded in 2007-2012, 6717 were linked: 5444 to a live birth record, 1306 to a stillbirth record, and 33 to both a live and stillbirth record. After identifying 2620 missed-matches and 124 false-matches, our estimated sensitivity was 72%, specificity was 88%, and positive predictive value was 98%. Linkage errors were associated with maternal education and self-identified race; women with more than 7 years of education or who self-declared as Caucasian were more likely to link. Dengue status was not associated with linkage error. CONCLUSION: Despite not having unique identifiers to link mothers and birth outcomes, we demonstrated a high standard of linkage, with sensitivity and specificity values comparable to previous literature. Although there were no differences in the characteristics of dengue cases missed or included in our linked dataset, linkage error occurred disproportionally by some social-demographic characteristics, which should be taken into account in future analyses

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

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

An outbreak of SARS-CoV-2 in a public-facing office in England.

BACKGROUND: An outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with an attack rate of 55% (22/40 workers) occurred at a public-facing office in England from August to September 2021. Published evidence regarding outbreaks in office workplaces remains limited. AIMS: To describe an investigation of workplace- and worker-related risk factors following an outbreak of SARS-CoV-2 in a public-facing office. METHODS: The COVID-19 (coronavirus disease 2019) Outbreak Investigation to Understand Transmission (COVID-OUT) study undertook an investigation of the outbreak. This included surface sampling, occupational environmental assessment, molecular and serological testing of workers, and detailed questionnaires. RESULTS: Despite existing COVID-19 control measures, surface sampling conducted during a self-imposed 2-week temporary office closure identified viral contamination (10/60 samples, 17% positive), particularly in a small, shared security office (6/9, 67% positive) and on a window handle in one open-plan office. Targeted enhanced cleaning was, therefore, undertaken before the office reopened. Repeat surface sampling after this identified only one positive (2%) sample. Ventilation was deemed adequate using carbon dioxide monitoring (typically ≤1000 ppm). Twelve workers (30%) responded to the COVID-OUT questionnaire, and all had been vaccinated with two doses. One-third of respondents (4/12) reported direct physical or close contact with members of the public; of these, 75% (3/4) reported a divider/screen between themselves and members of the public. CONCLUSIONS: The results highlight the potential utility of surface sampling to identify SARS-CoV-2 control deficiencies and the importance of evolving, site-specific risk assessments with layered COVID-19 mitigation strategies

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

Zika virus infection in pregnancy: a protocol for the joint analysis of the prospective cohort studies of the ZIKAlliance, ZikaPLAN and ZIKAction consortia

Introduction: Zika virus (ZIKV) infection in pregnancy has been associated with microcephaly and severe neurological damage to the fetus. Our aim is to document the risks of adverse pregnancy and birth outcomes and the prevalence of laboratory markers of congenital infection in deliveries to women experiencing ZIKV infection during pregnancy, using data from European Commission-funded prospective cohort studies in 20 centres in 11 countries across Latin America and the Caribbean. / Methods and analysis: We will carry out a centre-by-centre analysis of the risks of adverse pregnancy and birth outcomes, comparing women with confirmed and suspected ZIKV infection in pregnancy to those with no evidence of infection in pregnancy. We will document the proportion of deliveries in which laboratory markers of congenital infection were present. Finally, we will investigate the associations of trimester of maternal infection in pregnancy, presence or absence of maternal symptoms of acute ZIKV infection and previous flavivirus infections with adverse outcomes and with markers of congenital infection. Centre-specific estimates will be pooled using a two-stage approach. / Ethics and dissemination: Ethical approval was obtained at each centre. Findings will be presented at international conferences and published in peer-reviewed open access journals and discussed with local public health officials and representatives of the national Ministries of Health, Pan American Health Organization and WHO involved with ZIKV prevention and control activities

Modulation of innate immune responses at birth by prenatal malaria exposure and association with malaria risk during the first year of life.

BACKGROUND: Factors driving inter-individual differences in immune responses upon different types of prenatal malaria exposure (PME) and subsequent risk of malaria in infancy remain poorly understood. In this study, we examined the impact of four types of PME (i.e., maternal peripheral infection and placental acute, chronic, and past infections) on both spontaneous and toll-like receptors (TLRs)-mediated cytokine production in cord blood and how these innate immune responses modulate the risk of malaria during the first year of life. METHODS: We conducted a birth cohort study of 313 mother-child pairs nested within the COSMIC clinical trial (NCT01941264), which was assessing malaria preventive interventions during pregnancy in Burkina Faso. Malaria infections during pregnancy and infants' clinical malaria episodes detected during the first year of life were recorded. Supernatant concentrations of 30 cytokines, chemokines, and growth factors induced by stimulation of cord blood with agonists of TLRs 3, 7/8, and 9 were measured by quantitative suspension array technology. Crude concentrations and ratios of TLR-mediated cytokine responses relative to background control were analyzed. RESULTS: Spontaneous production of innate immune biomarkers was significantly reduced in cord blood of infants exposed to malaria, with variation among PME groups, as compared to those from the non-exposed control group. However, following TLR7/8 stimulation, which showed higher induction of cytokines/chemokines/growth factors than TLRs 3 and 9, cord blood cells of infants with evidence of past placental malaria were hyper-responsive in comparison to those of infants not-exposed. In addition, certain biomarkers, which levels were significantly modified depending on the PME category, were independent predictors of either malaria risk (GM-CSF TLR7/8 crude) or protection (IL-12 TLR7/8 ratio and IP-10 TLR3 crude, IL-1RA TLR7/8 ratio) during the first year of life. CONCLUSIONS: These findings indicate that past placental malaria has a profound effect on fetal immune system and that the differential alterations of innate immune responses by PME categories might drive heterogeneity between individuals to clinical malaria susceptibility during the first year of life

Hearing aid effectiveness after aural rehabilitation - individual versus group (HEARING) trial: RCT design and baseline characteristics

<p>Abstract</p> <p>Background</p> <p>Hearing impairment is the most common body system disability in veterans. In 2008, nearly 520,000 veterans had a disability for hearing loss through the Department of Veterans Affairs (VA). Changes in eligibility for hearing aid services, along with the aging population, contributed to a greater than 300% increase in the number of hearing aids dispensed from 1996 to 2006. In 2006, the VA committed to having no wait times for patient visits while providing quality clinically-appropriate care. One approach to achieving this goal is the use of group visits as an alternative to individual visits. We sought to determine: 1) if group hearing aid fitting and follow-up visits were at least as effective as individual visits, and 2) whether group visits lead to cost savings through the six month period after the hearing aid fitting. We describe the rationale, design, and characteristics of the baseline cohort of the first randomized clinical trial to study the impact of group versus individual hearing aid fitting and follow-up visits.</p> <p>Methods</p> <p>Participants were recruited from the VA Puget Sound Health Care System Audiology Clinic. Eligible patients had no previous hearing aid use and monaural or binaural air-conduction hearing aids were ordered at the evaluation visit. Participants were randomized to receive the hearing aid fitting and the hearing aid follow-up in an individual or group visit. The primary outcomes were hearing-related function, measured with the first module of the Effectiveness of Aural Rehabilitation (Inner EAR), and hearing aid adherence. We tracked the total cost of planned and unplanned audiology visits over the 6-month interval after the hearing aid fitting.</p> <p>Discussion</p> <p>A cohort of 659 participants was randomized to receive group or individual hearing aid fitting and follow-up visits. Baseline demographic and self-reported health status and hearing-related measures were evenly distributed across the treatment arms.</p> <p>Outcomes after the 6-month follow-up period are needed to determine if group visits were as least as good as those for individual visits and will be reported in subsequent publication.</p> <p>Trial Registration</p> <p>NCT00260663</p