Evaluation of the BNT162b2 Covid-19 Vaccine in Children 5 to 11 Years of Age.

BACKGROUND: Safe, effective vaccines against coronavirus disease 2019 (Covid-19) are urgently needed in children younger than 12 years of age. METHODS: A phase 1, dose-finding study and an ongoing phase 2-3 randomized trial are being conducted to investigate the safety, immunogenicity, and efficacy of two doses of the BNT162b2 vaccine administered 21 days apart in children 6 months to 11 years of age. We present results for 5-to-11-year-old children. In the phase 2-3 trial, participants were randomly assigned in a 2:1 ratio to receive two doses of either the BNT162b2 vaccine at the dose level identified during the open-label phase 1 study or placebo. Immune responses 1 month after the second dose of BNT162b2 were immunologically bridged to those in 16-to-25-year-olds from the pivotal trial of two 30-µg doses of BNT162b2. Vaccine efficacy against Covid-19 at 7 days or more after the second dose was assessed. RESULTS: During the phase 1 study, a total of 48 children 5 to 11 years of age received 10 µg, 20 µg, or 30 µg of the BNT162b2 vaccine (16 children at each dose level). On the basis of reactogenicity and immunogenicity, a dose level of 10 µg was selected for further study. In the phase 2-3 trial, a total of 2268 children were randomly assigned to receive the BNT162b2 vaccine (1517 children) or placebo (751 children). At data cutoff, the median follow-up was 2.3 months. In the 5-to-11-year-olds, as in other age groups, the BNT162b2 vaccine had a favorable safety profile. No vaccine-related serious adverse events were noted. One month after the second dose, the geometric mean ratio of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing titers in 5-to-11-year-olds to those in 16-to-25-year-olds was 1.04 (95% confidence interval [CI], 0.93 to 1.18), a ratio meeting the prespecified immunogenicity success criterion (lower bound of two-sided 95% CI, >0.67; geometric mean ratio point estimate, ≥0.8). Covid-19 with onset 7 days or more after the second dose was reported in three recipients of the BNT162b2 vaccine and in 16 placebo recipients (vaccine efficacy, 90.7%; 95% CI, 67.7 to 98.3). CONCLUSIONS: A Covid-19 vaccination regimen consisting of two 10-µg doses of BNT162b2 administered 21 days apart was found to be safe, immunogenic, and efficacious in children 5 to 11 years of age. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04816643.).

Clinical Characteristics and Outcomes Among Travelers With Severe Dengue : A GeoSentinel Analysis.

BACKGROUND: Dengue virus is a flavivirus transmitted by Aedes mosquitoes and is an important cause of illness worldwide. Data on the severity of travel-associated dengue illness are limited. OBJECTIVE: To describe the epidemiology, clinical characteristics, and outcomes among international travelers with severe dengue or dengue with warning signs as defined by the 2009 World Health Organization classification (that is, complicated dengue). DESIGN: Retrospective chart review and analysis of travelers with complicated dengue reported to GeoSentinel from January 2007 through July 2022. SETTING: 20 of 71 international GeoSentinel sites. PATIENTS: Returning travelers with complicated dengue. MEASUREMENTS: Routinely collected surveillance data plus chart review with abstraction of clinical information using predefined grading criteria to characterize the manifestations of complicated dengue. RESULTS: Of 5958 patients with dengue, 95 (2%) had complicated dengue. Eighty-six (91%) patients had a supplemental questionnaire completed. Eighty-five of 86 (99%) patients had warning signs, and 27 (31%) were classified as severe. Median age was 34 years (range, 8 to 91 years); 48 (56%) were female. Patients acquired dengue most frequently in the Caribbean (n = 27 [31%]) and Southeast Asia (n = 21 [24%]). Frequent reasons for travel were tourism (46%) and visiting friends and relatives (32%). Twenty-one of 84 (25%) patients had comorbidities. Seventy-eight (91%) patients were hospitalized. One patient died of nondengue-related illnesses. Common laboratory findings and signs were thrombocytopenia (78%), elevated aminotransferase (62%), bleeding (52%), and plasma leakage (20%). Among severe cases, ophthalmologic pathology (n = 3), severe liver disease (n = 3), myocarditis (n = 2), and neurologic symptoms (n = 2) were reported. Of 44 patients with serologic data, 32 confirmed cases were classified as primary dengue (IgM+/IgG-) and 12 as secondary (IgM-/IgG+) dengue. LIMITATIONS: Data for some variables could not be retrieved by chart review for some patients. The generalizability of our observations may be limited. CONCLUSION: Complicated dengue is relatively rare in travelers. Clinicians should monitor patients with dengue closely for warning signs that may indicate progression to severe disease. Risk factors for developing complications of dengue in travelers need further prospective study. PRIMARY FUNDING SOURCE: Centers for Disease Control and Prevention, International Society of Travel Medicine, Public Health Agency of Canada, and GeoSentinel Foundation.

Immunogenicity of adjuvanted versus high-dose inactivated influenza vaccines in older adults: a randomized clinical trial.

BACKGROUND: Adjuvanted inactivated influenza vaccine (aIIV) and high-dose inactivated influenza vaccine (HD-IIV) are U.S.-licensed for adults aged ≥ 65 years. This study compared serum hemagglutination inhibition (HAI) antibody titers for the A(H3N2) and A(H1N1)pdm09 and B strains after trivalent aIIV3 and trivalent HD-IIV3 in an older adult population. RESULTS: The immunogenicity population included 342 participants who received aIIV3 and 338 participants who received HD-IIV3. The proportion of participants that seroconverted to A(H3N2) vaccine strains after allV3 (112 participants [32.8%]) was inferior to the proportion of participants that seroconverted after HD-IIV3 (130 participants [38.5%]) at day 29 after vaccination (difference, - 5.8%; 95%CI, - 12.9% to 1.4%). There were no significant differences between the vaccine groups in percent seroconversion to A(H1N1)pdm09 or B vaccine strains, in percent seropositivity for any of the strains, or in post-vaccination GMT for the A(H1N1)pdm09 strain. The GMTs for the post-vaccination A(H3N2) and B strains were higher after HD-IIV than after aIIV3. CONCLUSIONS: Overall immune responses were similar after aIIV3 and HD-IIV3. For the primary outcome, the aIIV3 seroconversion rate for H3N2 did not meet noninferiority criteria compared with HD-IIV3, but the HD-IIV3 seroconversion rate was not statistically superior to the aIIV3 seroconversion rate. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03183908.

Comparison of Anti-SARS-CoV-2-Specific Antibody Signatures in Maternal and Infant Blood after COVID-19 Infection versus COVID-19 Vaccination during Pregnancy.

OBJECTIVE: The Advisory Committee on Immunization Practices and The American College of Obstetricians and Gynecologists recommend coronavirus disease 2019 (COVID-19) vaccine for pregnant persons to prevent severe illness and death. The objective was to examine levels of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG, IgM, and IgA against spike protein receptor binding domain (RBD) and nucleocapsid protein (NCP) in maternal and infant/cord blood at delivery after COVID 19 vaccination compared with SARS-CoV-2 infection at in mother-infant dyads at specified time points. STUDY DESIGN: Mothers with SARS-CoV-2 infection (n = 31) or COVID-19 vaccination (n = 25) during pregnancy were enrolled between July 2020 and November 2021. Samples were collected at delivery and IgG, IgM, and IgA to RBD of spike and NCPs compared in the infected and vaccinated groups. Timing of infection/vaccination prior to delivery and correlation with antibody levels was performed. RESULTS: The majority of participants received vaccination within 90 days of delivery and over half received the Pfizer BioNTech vaccine. There were no significant correlations between antibody levels and timing of infection or vaccination. Infant IgG levels to the RBD domain of spike protein were higher in the vaccinated group (n = 25) as compared with the infants born to mothers with infection (n = 31). Vaccination against COVID-19 during pregnancy was associated with detectable maternal and infant anti-RBD IgG levels at delivery irrespective of the timing of vaccination. CONCLUSION: Timing of vaccination had no correlation to the antibody levels suggesting that the timing of maternal vaccination in the cohort did not matter. There was no IgM detected in infants from vaccinated mothers. Infants from vaccinated mothers had robust IgG titers to RBD, which have a lasting protective effect in infants. KEY POINTS: · COVID-19 vaccination during pregnancy had detectable antibody.. · No correlation between antibody levels and timing of vaccination.. · Infants from vaccinated mothers had robust IgG titers to RBD..

SARS-CoV-2 in infant urine and fecal samples after in utero COVID-19 exposure.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a pandemic that has and will continue to affect many pregnant women. Knowledge regarding the risk of vertical transmission is limited. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) real-time reverse transcriptase-polymerase chain reaction (RT-PCR) of nasopharyngeal swabs typically have been used to confirm the diagnosis among infants, but whether the virus can be detected in other biological specimens, and therefore potentially transmitted in other ways, is unknown. Positive SARS-CoV-2 RT-PCR has been reported from feces and urine from adult patients. We hypothesize that the presence of SARS-CoV-2 in infant urine and fecal samples after prenatal COVID-19 exposure is low. METHODS: We examined the presence of SARS-CoV-2 RNA using RT-PCR in urine and fecal samples among 42 infants born to SARS-CoV-2-infected mothers during different stages of pregnancy. RESULTS: A urine sample was collected from 39 of 42 infants and fecal samples from all 42 infants shortly after birth. Although the majority of the women had the symptomatic disease (85.6%), we were unable to detect the presence of SARS-CoV-2 virus from any infant urine or fecal samples. CONCLUSIONS: SARS-CoV-2 was not detected in infant urine or feces after maternal infection during pregnancy, providing further evidence for low rates of perinatal transmission. IMPACT: SARS-CoV-2 was not detected in the urine or feces of infants of mothers with COVID-19 during various time points in pregnancy. This study provides further evidence for low rates of perinatal transmission of SARS-CoV-2. Results help to provide guidance on perinatal care practices for infants exposed to COVID-19 in utero.

Myocarditis Cases Reported After mRNA-Based COVID-19 Vaccination in the US From December 2020 to August 2021.

Importance: Vaccination against COVID-19 provides clear public health benefits, but vaccination also carries potential risks. The risks and outcomes of myocarditis after COVID-19 vaccination are unclear. Objective: To describe reports of myocarditis and the reporting rates after mRNA-based COVID-19 vaccination in the US. Design, Setting, and Participants: Descriptive study of reports of myocarditis to the Vaccine Adverse Event Reporting System (VAERS) that occurred after mRNA-based COVID-19 vaccine administration between December 2020 and August 2021 in 192 405 448 individuals older than 12 years of age in the US; data were processed by VAERS as of September 30, 2021. Exposures: Vaccination with BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna). Main Outcomes and Measures: Reports of myocarditis to VAERS were adjudicated and summarized for all age groups. Crude reporting rates were calculated across age and sex strata. Expected rates of myocarditis by age and sex were calculated using 2017-2019 claims data. For persons younger than 30 years of age, medical record reviews and clinician interviews were conducted to describe clinical presentation, diagnostic test results, treatment, and early outcomes. Results: Among 192 405 448 persons receiving a total of 354 100 845 mRNA-based COVID-19 vaccines during the study period, there were 1991 reports of myocarditis to VAERS and 1626 of these reports met the case definition of myocarditis. Of those with myocarditis, the median age was 21 years (IQR, 16-31 years) and the median time to symptom onset was 2 days (IQR, 1-3 days). Males comprised 82% of the myocarditis cases for whom sex was reported. The crude reporting rates for cases of myocarditis within 7 days after COVID-19 vaccination exceeded the expected rates of myocarditis across multiple age and sex strata. The rates of myocarditis were highest after the second vaccination dose in adolescent males aged 12 to 15 years (70.7 per million doses of the BNT162b2 vaccine), in adolescent males aged 16 to 17 years (105.9 per million doses of the BNT162b2 vaccine), and in young men aged 18 to 24 years (52.4 and 56.3 per million doses of the BNT162b2 vaccine and the mRNA-1273 vaccine, respectively). There were 826 cases of myocarditis among those younger than 30 years of age who had detailed clinical information available; of these cases, 792 of 809 (98%) had elevated troponin levels, 569 of 794 (72%) had abnormal electrocardiogram results, and 223 of 312 (72%) had abnormal cardiac magnetic resonance imaging results. Approximately 96% of persons (784/813) were hospitalized and 87% (577/661) of these had resolution of presenting symptoms by hospital discharge. The most common treatment was nonsteroidal anti-inflammatory drugs (589/676; 87%). Conclusions and Relevance: Based on passive surveillance reporting in the US, the risk of myocarditis after receiving mRNA-based COVID-19 vaccines was increased across multiple age and sex strata and was highest after the second vaccination dose in adolescent males and young men. This risk should be considered in the context of the benefits of COVID-19 vaccination.

Mother-Infant Dyads with COVID-19 at an Urban, Safety-Net Hospital: Clinical Manifestations and Birth Outcomes.

OBJECTIVE: This study aimed to describe maternal characteristics and clinical outcomes of infants born to mothers with positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) tests during pregnancy at an urban, safety-net hospital in Boston. STUDY DESIGN: We abstracted electronic chart data from 75 pregnant women with positive SARS-CoV-2 tests at any stage of gestation until 72 hours after birth who delivered consecutively between March 31 and August 6, 2020 at our center. We collected clinical data on maternal and infant characteristics, including testing, signs, and symptoms of coronavirus disease 2019 (COVID-19), delivery outcomes, newborn care practices (skin-to-skin care, location of care, and breastfeeding) and 30-day postdischarge infant emergency room visits and readmissions. We described categorical characteristics as percentages for this case series. RESULTS: Among 75 pregnant women, 47 (63%) were Hispanic, 10 (13%) had hypertension, 23 (30%) had prepregnancy obesity, and 57 (76%) had symptomatic SARS-CoV-2 infection. Regarding birth outcomes, 32 (41%) had cesarean delivery and 14 (19%) had preterm birth. Among 75 infants, 5 (7%) had positive SARS-CoV-2 polymerase chain reaction tests in the first week of life, all of whom were born to Hispanic mothers with symptomatic SARS-CoV-2 infection and had clinical courses consistent with gestational age. Six (8%) infants visited the emergency department within 30 days of discharge; one was admitted with a non-COVID-19 diagnosis. CONCLUSION: At our urban, safety-net hospital among pregnant women with positive SARS-CoV-2 tests, 41% had a cesarean delivery and 19% had a preterm birth. Seven percent of infants had one or more positive SARS-CoV-2 tests and all infants had clinical courses expected for gestational age. KEY POINTS: · Among 75 pregnant women with SARS-CoV-2 positive testing at our center, five infants (7%) had one or more SARS-CoV-2 positive tests in the first week of life.. · Infants with positive SARS-CoV-2 tests had clinical courses expected for gestational age..

Multisystem Inflammatory Syndrome in an Adult With COVID-19-A Trial of Anakinra: A Case Report.

COVID-19 disease has been a pandemic caused by a ß-coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A life-threatening multisystem inflammatory syndrome (MIS), secondary to SARS-CoV-2 virus infection, sharing common features with Kawasaki disease shock syndrome, staphylococcal/streptococcal shock syndrome, and macrophage activation syndrome in pediatric patients has been described. A total of 27 cases in adults (MIS-A) with a similar presentation have been reported so far. Here we describe the case of a 21-year-old man admitted with abdominal pain, diarrhea, tachycardia, and low blood pressure. He had elevated troponin, ferritin, and interleukin-2 receptor levels and had evidence of myocarditis. He tested positive for SARS-CoV-2 IgG antibody, and a diagnosis of MIS-A was made. Our case adds to the scant literature on this topic, and to our knowledge, it is the first case where anakinra was administered. He recovered well. MIS-A should be considered when young adults present with multiorgan dysfunction.

Area of exposure and treatment challenges of malaria in Eritrean migrants: a GeoSentinel analysis.

BACKGROUND: Recent reports highlight malaria as a frequent diagnosis in migrants who originate from Eritrea. A descriptive analysis of GeoSentinel cases of malaria in Eritrean migrants was done together with a literature review to elucidate key attributes of malaria in this group with a focus on possible areas of acquisition of malaria and treatment challenges. RESULTS: A total of 146 cases were identified from the GeoSentinel database from 1999 through September 2017, with a marked increase in 2014 and 2015. All patients originated from Eritrea and the main reporting GeoSentinel sites were in Norway, Switzerland, Sweden, Israel and Germany. The majority of patients (young adult males) were diagnosed with malaria following arrival in the host country. All patients had a possible exposure in Eritrea, but may have been exposed in documented transit countries including Ethiopia, Sudan and possibly Libya in detention centres. Most infections were due to Plasmodium vivax (84.2%), followed by Plasmodium falciparum (8.2%). Two patients were pregnant, and both had P. vivax malaria. Some 31% of the migrants reported having had malaria while in transit. The median time to onset of malaria symptoms post arrival in the host country was 39 days. Some 66% of patients were hospitalized and nine patients had severe malaria (according to WHO criteria), including five due to P. vivax. CONCLUSIONS: The 146 cases of mainly late onset, sometimes severe, P. vivax malaria in Eritrean migrants described in this multi-site, global analysis reflect the findings of single-centre analyses identified in the literature search. Host countries receiving asylum-seekers from Eritrea need to be prepared for large surges in vivax and, to a lesser extent, falciparum malaria, and need to be aware and prepared for glucose-6-phosphate dehydrogenase deficiency testing and primaquine treatment, which is difficult to procure and mainly unlicensed in Europe. There is an urgent need to explore the molecular epidemiology of P. vivax in Eritrean asylum-seekers, to investigate the area of acquisition of P. vivax along common transit routes and to determine whether there has been re-introduction of malaria in areas, such as Libya, where malaria is considered eliminated, but where capable vectors and Plasmodium co-circulate.

Travel-Associated Zika Virus Disease Acquired in the Americas Through February 2016: A GeoSentinel Analysis.

Background: Zika virus has spread rapidly in the Americas and has been imported into many nonendemic countries by travelers. Objective: To describe clinical manifestations and epidemiology of Zika virus disease in travelers exposed in the Americas. Design: Descriptive, using GeoSentinel records. Setting: 63 travel and tropical medicine clinics in 30 countries. Patients: Ill returned travelers with a confirmed, probable, or clinically suspected diagnosis of Zika virus disease seen between January 2013 and 29 February 2016. Measurements: Frequencies of demographic, trip, and clinical characteristics and complications. Results: Starting in May 2015, 93 cases of Zika virus disease were reported. Common symptoms included exanthema (88%), fever (76%), and arthralgia (72%). Fifty-nine percent of patients were exposed in South America; 71% were diagnosed in Europe. Case status was established most commonly by polymerase chain reaction (PCR) testing of blood and less often by PCR testing of other body fluids or serology and plaque-reduction neutralization testing. Two patients developed Guillain-Barré syndrome, and 3 of 4 pregnancies had adverse outcomes (microcephaly, major fetal neurologic abnormalities, and intrauterine fetal death). Limitation: Surveillance data collected by specialized clinics may not be representative of all ill returned travelers, and denominator data are unavailable. Conclusion: These surveillance data help characterize the clinical manifestations and adverse outcomes of Zika virus disease among travelers infected in the Americas and show a need for global standardization of diagnostic testing. The serious fetal complications observed in this study highlight the importance of travel advisories and prevention measures for pregnant women and their partners. Travelers are sentinels for global Zika virus circulation and may facilitate further transmission. Primary Funding Source: Centers for Disease Control and Prevention, International Society of Travel Medicine, and Public Health Agency of Canada.

Measles in the 21st Century, a Continuing Preventable Risk to Travelers: Data From the GeoSentinel Global Network.

Measles remains a risk for travelers, with 94 measles diagnoses reported to the GeoSentinel network from 2000 to 2014, two-thirds since 2010. Asia was the most common exposure region, then Africa and Europe. Efforts to reduce travel-associated measles should target all vaccine-eligible travelers, including catch-up vaccination of susceptible adults.

Profile of illness in Syrian refugees: A GeoSentinel analysis, 2013 to 2015.

Screening of 488 Syrian unaccompanied minor refugees (< 18 years-old) in Berlin showed low prevalence of intestinal parasites (Giardia, 7%), positive schistosomiasis serology (1.4%) and absence of hepatitis B. Among 44 ill adult Syrian refugees examined at GeoSentinel clinics worldwide, cutaneous leishmaniasis affected one in three patients; other noteworthy infections were active tuberculosis (11%) and chronic hepatitis B or C (9%). These data can contribute to evidence-based guidelines for infectious disease screening of Syrian refugees.

GeoSentinel surveillance of illness in returned travelers, 2007-2011.

BACKGROUND: International travel continues to increase, particularly to Asia and Africa. Clinicians are increasingly likely to be consulted for advice before travel or by ill returned travelers. OBJECTIVE: To describe typical diseases in returned travelers according to region, travel reason, and patient demographic characteristics; describe the pattern of low-frequency travel-associated diseases; and refine key messages for care before and after travel. DESIGN: Descriptive, using GeoSentinel records. SETTING: 53 tropical or travel disease units in 24 countries. PATIENTS: 42 173 ill returned travelers seen between 2007 and 2011. MEASUREMENTS: Frequencies of demographic characteristics, regions visited, and illnesses reported. RESULTS: Asia (32.6%) and sub-Saharan Africa (26.7%) were the most common regions where illnesses were acquired. Three quarters of travel-related illness was due to gastrointestinal (34.0%), febrile (23.3%), and dermatologic (19.5%) diseases. Only 40.5% of all ill travelers reported pretravel medical visits. The relative frequency of many diseases varied with both travel destination and reason for travel, with travelers visiting friends and relatives in their country of origin having both a disproportionately high burden of serious febrile illness and very low rates of advice before travel (18.3%). Life-threatening diseases, such as Plasmodium falciparum malaria, melioidosis, and African trypanosomiasis, were reported. LIMITATIONS: Sentinel surveillance data collected by specialist clinics do not reflect healthy returning travelers or those with mild or self-limited illness. Data cannot be used to infer quantitative risk for illness. CONCLUSION: Many illnesses may have been preventable with appropriate advice, chemoprophylaxis, or vaccination. Clinicians can use these 5-year GeoSentinel data to help tailor more efficient pretravel preparation strategies and evaluate possible differential diagnoses of ill returned travelers according to destination and reason for travel. PRIMARY FUNDING SOURCE: Centers for Disease Control and Prevention.

Chagas cardiomyopathy in Boston, Massachusetts: Identifying disease and improving management after community and hospital-based screening.

BACKGROUND: Limited data exist regarding cardiac manifestations of Chagas disease in migrants living in non-endemic regions. METHODS: A retrospective cohort analysis of 109 patients with Chagas disease seen at Boston Medical Center (BMC) between January 2016 and January 2023 was performed. Patients were identified by screening and testing migrants from endemic regions at a community health center and BMC. Demographic, laboratory, and cardiac evaluation data were collected. RESULTS: Mean age of the 109 patients was 43 years (range 19-76); 61% were female. 79% (86/109) were diagnosed with Chagas disease via screening and 21% (23/109) were tested given symptoms or electrocardiogram abnormalities. Common symptoms included palpitations (25%, 27/109) and chest pain (17%, 18/109); 52% (57/109) were asymptomatic. Right bundle branch block (19%, 19/102), T-wave changes (18%, 18/102), and left anterior fascicular block (11%, 11/102) were the most common electrocardiogram abnormalities; 51% (52/102) had normal electrocardiograms. Cardiomyopathy stage was ascertained in 94 of 109 patients: 51% (48/94) were indeterminate stage A and 49% (46/94) had cardiac structural disease (stages B1-D). Clinical findings that required clinical intervention or change in management were found in 23% (25/109), and included cardiomyopathy, apical hypokinesis/aneurysm, stroke, atrial or ventricular arrhythmias, and apical thrombus. CONCLUSIONS: These data show high rates of cardiac complications in a cohort of migrants living with Chagas disease in a non-endemic setting. We demonstrate that Chagas disease diagnosis prompts cardiac evaluation which often identifies actionable cardiac disease and provides opportunities for prevention and treatment.

Bivalent Omicron BA.4/BA.5 BNT162b2 Vaccine in 6-Month- to <12-Year-Olds.

BACKGROUND: With the future epidemiology and evolution of SARS-CoV-2 uncertain, use of safe and effective COVID-19 vaccines in pediatric populations remains important. METHODS: We report data from two open-label substudies of an ongoing phase 1/2/3 master study (NCT05543616) investigating safety and immunogenicity of a variant-adapted bivalent COVID-19 vaccine encoding ancestral and Omicron BA.4/BA.5 spike proteins (bivalent BNT162b2). The open-label groups presented here evaluate dose 4 with bivalent BNT162b2 in 6-month-<12-year-olds who previously received three original (monovalent) BNT162b2 doses. In 6-month-<5-year-olds, primary immunogenicity objectives were to demonstrate superiority (neutralizing titer) and noninferiority (seroresponse rate) to Omicron BA.4/BA.5 and noninferiority (neutralizing titer and seroresponse rate) to SARS-CoV-2 ancestral strains in participants who received bivalent BNT162b2 dose 4 compared with a matched group who received three doses of original BNT162b2 in the pivotal pediatric study (NCT04816643). In 5-<12-year-olds, primary immunogenicity comparisons were descriptive. Reactogenicity and safety following vaccination were evaluated. RESULTS: In 6-month-<5-year-olds, dose 4 with bivalent BNT162b2 met predefined immunogenicity superiority and noninferiority criteria against Omicron BA.4/BA.5 and ancestral strains when compared with dose 3 of original BNT162b2. In 5-<12-year-olds, bivalent BNT162b2 induced robust Omicron BA.4/BA.5 and ancestral strain neutralizing titers comparable to dose 3 of original BNT162b2. The safety profile for dose 4 of bivalent BNT162b2 given as dose 4 was consistent with that of original BNT162b2 in 6 month-<12-year-olds. Reactogenicity events were generally mild-to-moderate. No adverse events led to discontinuation. CONCLUSIONS: These safety and immunogenicity data support a favorable benefit-risk profile for a variant-adapted BNT162b2 in children <12 years old.

Spectrum of illness in international migrants seen at GeoSentinel clinics in 1997-2009, part 1: US-bound migrants evaluated by comprehensive protocol-based health assessment.

BACKGROUND: Many nations are struggling to develop structured systems and guidelines to optimize the health of new arrivals, but there is currently no international consensus about the best approach. METHODS: Data on 7792 migrants who crossed international borders for the purpose of resettlement and underwent a protocol-based health assessment were collected from the GeoSentinel Surveillance network. Demographic and health characteristics of a subgroup of these migrants seen at 2 US-based GeoSentinel clinics for protocol-based health assessments are described. RESULTS: There was significant variation over time in screened migrant populations and in their demographic characteristics. Significant diagnoses identified in all migrant groups included latent tuberculosis, found in 43% of migrants, eosinophilia in 15%, and hepatitis B infection in 6%. Variation by region occurred for select diagnoses such as parasitic infections. Notably absent were infectious tuberculosis, soil-transmitted helminths, and malaria. Although some conditions would be unfamiliar to clinicians in receiving countries, universal health problems such as dental caries, anemia, ophthalmologic conditions, and hypertension were found in 32%, 11%, 10%, and 5%, respectively, of screened migrants. CONCLUSIONS: Data from postarrival health assessments can inform clinicians about screening tests to perform in new immigrants and help communities prepare for health problems expected in specific migrant populations. These data support recommendations developed in some countries to screen all newly arriving migrants for some specific diseases (such as tuberculosis) and can be used to help in the process of developing additional screening recommendations that might be applied broadly or focused on specific at-risk populations.

Spectrum of illness in international migrants seen at GeoSentinel clinics in 1997-2009, part 2: migrants resettled internationally and evaluated for specific health concerns.

BACKGROUND: Increasing international migration may challenge healthcare providers unfamiliar with acute and long latency infections and diseases common in this population. This study defines health conditions encountered in a large heterogenous group of migrants. METHODS: Migrants seen at GeoSentinel clinics for any reason, other than those seen at clinics only providing comprehensive protocol-based health screening soon after arrival, were included. Proportionate morbidity for syndromes and diagnoses by country or region of origin were determined and compared. RESULTS: A total of 7629 migrants from 153 countries were seen at 41 GeoSentinel clinics in 19 countries. Most (59%) were adults aged 19-39 years; 11% were children. Most (58%) were seen >1 year after arrival; 27% were seen after >5 years. The most common diagnoses were latent tuberculosis (22%), viral hepatitis (17%), active tuberculosis (10%), human immunodeficiency virus (HIV)/AIDS (7%), malaria (7%), schistosomiasis (6%), and strongyloidiasis (5%); 5% were reported healthy. Twenty percent were hospitalized (24% for active tuberculosis and 21% for febrile illness [83% due to malaria]), and 13 died. Tuberculosis diagnoses and HIV/AIDS were reported from all regions, strongyloidiasis from most regions, and chronic hepatitis B virus (HBV) particularly in Asian immigrants. Regional diagnoses included schistosomiasis (Africa) and Chagas disease (Americas). CONCLUSIONS: Eliciting a migration history is important at every encounter; migrant patients may have acute illness or chronic conditions related to exposure in their country of origin. Early detection and treatment, particularly for diagnoses related to tuberculosis, HBV, Strongyloides, and schistosomiasis, may improve outcomes. Policy makers should consider expansion of refugee screening programs to include all migrants.

Drinking Water From Private Wells and Risks to Children.

Drinking water for >23 million US households is obtained from private wells. These wells can become contaminated by chemicals, naturally occurring toxic substances, or pathogenic organisms that can cause illness in children. Although the US Environmental Protection Agency and most states offer some guidance for the construction, maintenance, and testing of private wells, most states only regulate the construction of new private water wells. With few exceptions, well owners are responsible for their own wells after the initial construction. Children may also drink well water at childcare or when traveling. This policy statement provides recommendations for the inspection, testing, and remediation of private wells to provide safe drinking water for children.

Drinking Water From Private Wells and Risks to Children.

Drinking water for approximately 23 million US households is obtained from private wells. These wells can become contaminated by pollutant chemicals or pathogenic organisms, leading to significant illness. Although the US Environmental Protection Agency and all states offer guidance for construction, maintenance, and testing of private wells, most states only regulate the construction of new private water wells. With a few exceptions, there is little regulation after construction. Well owners are responsible for their own wells. Children may also drink well water at child care or when traveling. Illness resulting from children's ingestion of contaminated water can be severe. This report reviews relevant aspects of groundwater and wells; describes the common chemical and microbiologic contaminants; gives an algorithm with recommendations for inspection, testing, and remediation for wells providing drinking water for children; and provides references and Internet resources for more information.

Maternal, Infant, and Breast Milk Antibody Response Following COVID-19 Infection in Early Versus Late Gestation.

BACKGROUND: Coronavirus disease 2019 [severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)] infection at varying time points during the pregnancy can influence antibody levels after delivery. We aimed to examine SARS-CoV-2 IgG, IgM and IgA receptor binding domain of the spike protein and nucleocapsid protein (N-protein) reactive antibody concentrations in maternal blood, infant blood and breastmilk at birth and 6 weeks after SARS-CoV-2 infection in early versus late gestation. METHODS: Mothers with SARS-CoV-2 infection during pregnancy were enrolled between July 2020 and May 2021. Maternal blood, infant blood and breast milk samples were collected at delivery and 6 weeks postpartum. Samples were analyzed for SARS-CoV-2 spike and N-protein reactive IgG, IgM and IgA antibodies. Antibody concentrations were compared at the 2 time points and based on trimester of infection ("early" 1st/2nd vs. "late" 3rd). RESULTS: Dyads from 20 early and 11 late trimester infections were analyzed. For the entire cohort, there were no significant differences in antibody levels at delivery versus 6 weeks with the exception of breast milk levels which declined over time. Early gestation infections were associated with higher levels of breastmilk IgA to spike protein ( P = 0.04). Infant IgG levels to spike protein were higher at 6 weeks after late infections ( P = 0.04). There were strong correlations between maternal and infant IgG levels at delivery ( P < 0.01), and between breastmilk and infant IgG levels. CONCLUSIONS: SARS-CoV-2 infection in early versus late gestation leads to a persistent antibody response in maternal blood, infant blood and breast milk over the first 6 weeks after delivery.