Nonsecretor Phenotype Is Associated With Less Risk of Rotavirus-Associated Acute Gastroenteritis in a Vaccinated Nicaraguan Birth Cohort.

BACKGROUND: Histo-blood group antigens (HBGAs) have been associated with rotavirus vaccine take; but the effect of these HBGAs on rotavirus incidence and risk remains poorly explored in vaccinated populations. METHODS: Rotavirus-associated acute gastroenteritis (AGE) was assessed in 444 Nicaraguan children followed from birth until 3 years of age. AGE episodes were tested for rotavirus by reverse-transcription quantitative polymerase chain reaction, and saliva or blood was used to determine HBGA phenotypes. Cox proportional hazards models were used to estimate the relative hazard of rotavirus AGE by HBGA phenotypes. RESULTS: Rotavirus was detected in 109 (7%) stool samples from 1689 AGE episodes over 36 months of observation between June 2017 and July 2021. Forty-six samples were successfully genotyped. Of these, 15 (35%) were rotavirus vaccine strain G1P[8], followed by G8P[8] or G8P[nt] (11 [24%]) and equine-like G3P[8] (11 [24%]). The overall incidence of rotavirus-associated AGE was 9.2 per 100 child-years, and was significantly higher in secretor than nonsecretor children (9.8 vs 3.5/100 child-years, P = .002). CONCLUSIONS: The nonsecretor phenotype was associated with decreased risk of clinical rotavirus vaccine failure in a vaccinated Nicaraguan birth cohort. These results show the importance of secretor status on rotavirus risk, even in vaccinated children.

Epigenome-wide methylation and progression to high-grade cervical intraepithelial neoplasia (CIN2+): a prospective cohort study in the United States.

BACKGROUND: Methylation levels may be associated with and serve as markers to predict risk of progression of precancerous cervical lesions. We conducted an epigenome-wide association study (EWAS) of CpG methylation and progression to high-grade cervical intraepithelial neoplasia (CIN2 +) following an abnormal screening test. METHODS: A prospective US cohort of 289 colposcopy patients with normal or CIN1 enrollment histology was assessed. Baseline cervical sample DNA was analyzed using Illumina HumanMethylation 450K (n = 76) or EPIC 850K (n = 213) arrays. Participants returned at provider-recommended intervals and were followed up to 5 years via medical records. We assessed continuous CpG M values for 9 cervical cancer-associated genes and time-to-progression to CIN2+. We estimated CpG-specific time-to-event ratios (TTER) and hazard ratios using adjusted, interval-censored Weibull accelerated failure time models. We also conducted an exploratory EWAS to identify novel CpGs with false discovery rate (FDR) < 0.05. RESULTS: At enrollment, median age was 29.2 years; 64.0% were high-risk HPV-positive, and 54.3% were non-white. During follow-up (median 24.4 months), 15 participants progressed to CIN2+. Greater methylation levels were associated with a shorter time-to-CIN2+ for CADM1 cg03505501 (TTER = 0.28; 95%CI 0.12, 0.63; FDR = 0.03) and RARB Cluster 1 (TTER = 0.46; 95% CI 0.29, 0.71; FDR = 0.01). There was evidence of similar trends for DAPK1 cg14286732, PAX1 cg07213060, and PAX1 Cluster 1. The EWAS detected 336 novel progression-associated CpGs, including those located in CpG islands associated with genes FGF22, TOX, COL18A1, GPM6A, XAB2, TIMP2, GSPT1, NR4A2, and APBB1IP. CONCLUSIONS: Using prospective time-to-event data, we detected associations between CADM1-, DAPK1-, PAX1-, and RARB-related CpGs and cervical disease progression, and we identified novel progression-associated CpGs. IMPACT: Methylation levels at novel CpG sites may help identify individuals with ≤CIN1 histology at higher risk of progression to CIN2+ and inform risk-based cervical cancer screening guidelines.

First Episodes of Norovirus and Sapovirus Gastroenteritis Protect Against Subsequent Episodes in a Nicaraguan Birth Cohort.

BACKGROUND: Norovirus and sapovirus cause a large burden of acute gastroenteritis (AGE) in young children. We assessed protection conferred by norovirus and sapovirus AGE episodes against future episodes. METHODS: Between June 2017 and July 2018, we recruited 444 newborns in León, Nicaragua. Weekly household surveys identified AGE episodes over 36 months, and AGE stools were tested by reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) for norovirus genogroup (G)I/GII and sapovirus. We used recurrent-event Cox models and negative control methods to estimate protection conferred by first episodes, controlling for observed and unobserved risk factors, respectively. RESULTS: Sapovirus episodes conferred a 69% reduced hazard of subsequent episodes using the negative control method. Norovirus GI (hazard ratio [HR] = 0.67; 95% confidence interval [CI] = 0.31, 1.3) and GII (HR = 0.20; 95% CI = 0.04, 0.44) episodes also appeared highly protective. Protection against norovirus GII was enhanced following two episodes. CONCLUSIONS: Evidence of natural immunity in early childhood provides optimism for the future success of pediatric norovirus and sapovirus vaccines.

Testing for Sexually Transmitted Infection Using Wet and Dry Self-Collected Brush Samples Among Women in Mombasa, Kenya.

ABSTRACT: We compared detection of Chlamydia trachomatis , Neisseria gonorrhoeae , and Trichomonas vaginalis using dry and wet self-collected samples using brushes among females who engage in sex work in Mombasa, Kenya. Detection of T. vaginalis and N. gonorrhoeae in dry and wet samples was similar, but C. trachomatis detection in dry samples appeared lower.

Health Care Provider Perceptions of Facilitators and Barriers to Human Papillomavirus Vaccination Delivery in Five Countries.

BACKGROUND: National human papillomavirus (HPV) vaccination programs could reduce global cervical cancer morbidity and mortality with support from health care providers. We assessed providers' perceptions of HPV vaccination in 5 countries. METHODS: We identified providers from 5 countries where national HPV vaccination programs were at various stages of implementation: Argentina, Malaysia, South Africa, South Korea, and Spain. Providers authorized to administer adolescent vaccines completed an in-depth survey, reporting perceptions of barriers and facilitators to initiating and completing HPV vaccination, and logistical challenges to HPV vaccination. RESULTS: Among 151 providers, common barriers to HPV vaccination initiation across all countries were parents' lack of awareness (39%), concerns about vaccine safety or efficacy (33%), and cost to patients (30%). Vaccination education campaign (70%) was the most commonly cited facilitator of HPV vaccination initiation. Common barriers to series completion included no reminder system or dosing schedule (37%), loss to follow-up or forgetting appointment (29%), and cost to patients (25%). Cited facilitators to completing the vaccine series were education campaigns (45%), affordable vaccination (32%), and reminder/recall systems (22%). Among all countries, high cost of vaccination was the most common logistical challenge to offering vaccination to adolescents (33%). CONCLUSIONS: Incorporating provider insights into future HPV vaccination programs could accelerate vaccine delivery to increase HPV vaccination rates globally.

Seroepidemiology of SARS-CoV-2 infections in an urban population-based cohort in León, Nicaragua.

In a Nicaraguan population-based cohort, SARS-CoV-2 seroprevalence reached 28% in the first 6 months of the country's epidemic and reached 35% 6 months later. Immune waning was uncommon. Individuals with a seropositive household member were over three times as likely to be seropositive themselves, suggesting the importance of household transmission.

Students with global experiences during medical school are more likely to work in settings that focus on the underserved: an observational study from a public U.S. institution.

BACKGROUND: Global health interest has grown among medical students over the past 20 years, and most medical schools offer global health opportunities. Studies suggest that completing global health electives during medical school may increase the likelihood of working with underserved populations in a clinical or research capacity. This study aimed to assess the association of global electives in medical school on subsequently working in global health and with underserved populations in the United States (U.S.), additionally considering students' interests and experiences prior to medical school. We also examined whether respondents perceived benefits gained from global electives. METHODS: We surveyed medical school graduates (classes of 2011-2015) from a large public medical school in the U.S. to describe current practice settings and previous global health experience. We evaluated work, volunteer, and educational experiences preceding medical school, socioeconomic status, race and ethnicity using American Medical College Application Service (AMCAS) data. We assessed the association between students' backgrounds, completing global health electives in medical school and current work in global health or with underserved populations in the U.S. RESULTS: In the 5 to 8 years post-graduation, 78% of 161 respondents reported work, research, or teaching with a focus on global or underserved U.S. POPULATIONS: Completing a global health elective during medical school (p = 0.0002) or during residency (p = 0.06) were positively associated with currently working with underserved populations in the U.S. and pre-medical school experiences were marginally associated (p = 0.1). Adjusting for pre-medical school experiences, completing a global health elective during medical school was associated with a 22% greater prevalence of working with an underserved population. Perceived benefits from global electives included improved cultural awareness, language skills, public health and research skills, and ability to practice in technology-limited settings. CONCLUSION: Medical school graduates who participated in global electives as students were more likely than their peers to pursue careers with underserved populations, independent of experiences prior to medical school. We hypothesize that by offering global health experiences, medical schools can enhance the interests and skills of graduates that will make them more likely and better prepared to work with underserved populations in the U.S. and abroad.

Association of State Legislation of Human Papillomavirus Vaccination with Vaccine Uptake Among Adolescents in the United States.

We assessed the association of state legislation with adolescent human papillomavirus (HPV) vaccination rates in states that legislated information dissemination or administration of HPV vaccination. Using insurance claims, we calculated monthly HPV vaccination rates (November 2009-December 2017) among adolescents in states that passed HPV vaccination legislation during that period: Missouri (July 2010), Kentucky (February 2012), Indiana (March 2013), Oregon (June 2013). We used segmented regression to estimate levels and trends of HPV vaccination rates, comparing pre-legislation to post-legislation segments, adjusting for seasonal vaccination patterns and changes to the vaccination recommendation among males during the study period. Indiana's legislation allowed pharmacists to administer HPV vaccination; legislation in Kentucky, Missouri, and Oregon included provisions HPV and cervical cancer education. No statistically significant increases in HPV vaccination levels or trends were observed in the post-legislation segments among adolescents overall; however, a significant post-legislation increase in vaccination trends was observed among boys in Missouri (ß = 0.16, p = 0.03). Evidence for a positive impact of legislation on HPV vaccination rates is limited. The scarcity of policies that directly facilitate or promote HPV vaccination, and the breadth of exemptions to school vaccination requirements, may limit the effectiveness of these policies. Continuing efforts to introduce and pass legislation that directly facilitates HPV vaccination, combined with promoting existing evidence-based interventions, can provide opportunities to identify the most effective strategies to increase adolescent HPV vaccination rates.

Overcoming barriers to adolescent vaccination: perspectives from vaccine providers in North Carolina.

To capture strategies for achieving high adolescent coverage of tetanus-diphtheria-acellular pertussis (Tdap), meningococcal conjugate (MenACWY), and human papillomavirus (HPV) vaccination, we surveyed employees of 20 North Carolina (N.C.) clinics that achieved adolescent vaccination coverage higher than the state average. One employee per clinic completed a surveysummarizing clinic practices regarding adolescent vaccination; perceived barriers and facilitators to Tdap/MenACWY/HPV vaccination; and the role of "champions" who made special efforts to promote adolescent vaccination. Common perceived barriers for all vaccinations were parental opposition and logistical barriers to receiving vaccination. For HPV vaccination, employees cited parental concerns about sexual behavior and injection site pain; no school vaccination requirement; and low-perceived benefit in boys. Most clinics (80%) implemented successful changes to increase adolescent vaccination: consistently offering vaccination, tracking vaccination status using existing data, providing appointment reminders, updating providers on vaccination recommendations, and expanding vaccination hours. Strategies to improve HPV vaccination included co-administration with Tdap and MenACWY, and providing reminders to complete the vaccination series. Vaccine champions strongly recommended vaccination to parents (55%) and educated parents on vaccination recommendations (36%). Clinics in N.C.and similar settings can implement these and other low-resource strategies to overcome adolescent vaccination barriers. ABBREVIATIONS: CDC=Centers for Disease Control and Prevention; EHR=Electronic health record; HPV=Human papillomavirus; Tdap=Tetanus-diphtheria-acellular pertussis vaccine; MenACWY=Meningococcal Conjugate Vaccine; NCIB=North Carolina Immunization Branch; NCIR=North Carolina Immunization Registry; ACIP=Advisory Committee on Immunization Practices.

Awareness, Knowledge, and Travel-Related Risk Factors for Zika Virus Among Latinas Attending a Federally Qualified Health Center in Rural North Carolina.

BACKGROUND The Zika virus (ZIKV) epidemic that began in 2015 presented a risk for ZIKV infection among persons who traveled to ZIKV-affected countries. Latinas in North Carolina and their sexual partners may be exposed to ZIKV when traveling to these regions.METHODS We administered a cross-sectional survey, measuring ZIKV risk and knowledge, to a convenience sample of 262 reproductive-age Latinas attending a Federally Qualified Health Center in rural North Carolina. We described ZIKV risk and knowledge in the sample, and compared responses between those who were pregnant or recently pregnant, and those who were not pregnant. We further identified factors associated with 1) awareness of ZIKV and 2) high knowledge of ZIKV sequelae and prevention among those who were aware of ZIKV, using log-binomial regression.RESULTS Two-thirds of participants had ever heard of ZIKV, which was positively associated with educational attainment. Most participants aware of ZIKV had moderate/high knowledge of ZIKV transmission (92.5%) and symptoms (73.2%), but knowledge of preventing sexual and congenital transmission was limited. Travel was infrequent among pregnant or recently pregnant participants (5.4%) and their partners (7.1%). Despite low risk for ZIKV infection, participants were willing to practice ZIKV prevention.LIMITATIONS Our study is limited by a lack of generalizability to Latinas in other regions of the country, self-reporting bias, and lack of survey validation as an indicator of English language proficiency.CONCLUSIONS Providers should identify patients likely to become pregnant and travel to high-risk areas, inquire about partner travel history, and offer culturally appropriate ZIKV risk counseling.

Acceptability of two- versus three-dose human papillomavirus vaccination schedule among providers and mothers of adolescent girls: a mixed-methods study in five countries.

PURPOSE: The World Health Organization revised its human papillomavirus (HPV) vaccination recommendations to include a two (2-) dose schedule for girls aged ≤ 15 years. We investigated acceptability of 2- versus 3-dose schedule among adolescent vaccination providers and mothers of adolescent girls in five countries. METHODS: Adolescent vaccination providers (N = 151) and mothers of adolescent girls aged 9-14 years (N = 118) were recruited from Argentina, Malaysia, South Africa, South Korea, and Spain. We assessed providers' preference for a 2- versus 3-dose HPV vaccination schedule via quantitative surveys. Mothers' attitudes towards a 2-dose schedule were assessed through focus group discussions. RESULTS: Most adolescent providers preferred a 2- over a 3-dose HPV vaccination schedule (overall: 74%), with preference ranging from 45.2% (South Africa) to 90.0% (South Korea). Lower cost, fewer clinic visits, and higher series completion were commonly cited reasons for 2-dose preference among providers and mothers. Safety and efficacy concerns were commonly cited barriers to accepting a 2-dose HPV vaccination schedule among providers and mothers. Mothers generally accepted the reduced schedule, however requested further information from a trusted source. CONCLUSIONS: Adolescent vaccination providers and mothers preferred the 2-dose over 3-dose HPV vaccination schedule. Acceptability of a 2-dose HPV vaccination could be improved with additional information to providers and mothers on HPV vaccination safety and efficacy.

Epstein-Barr Virus, High-Risk Human Papillomavirus and Abnormal Cervical Cytology in a Prospective Cohort of African Female Sex Workers.

BACKGROUND: High-oncogenic-risk human papillomavirus (hrHPV) is necessary, although insufficient, to promote cervical cancer. Like HPV, Epstein-Barr virus (EBV) is a common pathogen with the capacity to promote epithelial neoplasms. We examined the association between cervical EBV, hrHPV, and cytology in female sex workers in Nairobi, Kenya. METHODS: Women (n = 332) with known cervical cytology and hrHPV mRNA results were evaluated for cervical EBV DNA by conventional polymerase chain reaction. Prevalence ratios (PRs) were calculated to assess the relationships between EBV, hrHPV, and cervical cytology. Prospective analyses used risk ratios and time-to-event analyses to determine the association of EBV with hrHPV clearance and with abnormal cytology outcomes. RESULTS: Baseline prevalence of hrHPV and EBV was 29% and 19%, respectively. Higher EBV prevalence was found among women with older age, HIV, hrHPV, abnormal cytology, Mycoplasma genitalium infection, smoking habits, younger age at sexual debut, and less frequent condom use. At baseline, women with EBV had a higher prevalence of hrHPV infection than did EBV-negative women (52% vs. 24%; HIV-adjusted PR [95% confidence interval], 1.8 [1.3-2.6]). Epstein-Barr virus-positive women had a higher prevalence than did EBV-negative women of high-grade precancer (15% vs. 2%) and abnormal cytology (37% vs. 15%), although HIV- and hrHPV-adjusted associations were not significant (high-grade precancer: PR, 2.0 [0.7-5.9]; abnormal cytology: PR, 1.4 [0.9-2.2]). In prospective analyses, a marginal association was observed between baseline EBV detection and delayed hrHPV clearance. CONCLUSIONS: Our data support a possible role for EBV as a high-risk marker or cofactor for HPV-mediated cervical cancer development.

Transmission Patterns of Norovirus From Infected Children to Household Members in León, Nicaragua.

Norovirus is a common and highly transmissible gastrointestinal pathogen. Among 34 Nicaraguan households with a norovirus-infected child, 48% experienced norovirus transmission within 1 week, infecting 18% of household members; GII norovirus was more commonly transmitted than GI. Pediatric norovirus vaccines could prevent both index cases and transmission to close contacts.

Patterns of use of recombinant zoster vaccine among commercially-insured immunocompetent and immunocompromised adults 50-64 years old in the United States.

PURPOSE: The Centers for Disease Control and Prevention (CDC) recommends recombinant zoster vaccination (RZV) for adults ≥ 50 years to prevent herpes zoster (HZ) and its sequelae. Initially, no distinct recommendation was made for immunocompromised adults, who experience higher HZ rates and more severe outcomes. We characterized receipt of first RZV dose (initiation) and both doses (completion) over time, and the impact of immune function on RZV uptake among adults aged 50-64 years in the United States. METHODS: We identified RZV claims from the IBM MarketScan database between 1/1/2018 and 12/31/2019. We characterized immunocompromised enrollees as having malignancy, HIV, solid organ transplant, primary immunosuppression, or medication-induced immunosuppression using inpatient, outpatient, and prescription claims in the 6 months prior to study start. We evaluated patterns of vaccine uptake by demographic and healthcare access characteristics and immune status. RESULTS: The cumulative incidence of RZV initiation during the study period was 10.0%. Incidence increased with age and number of medical office visits, and was higher among women, urban residents, high-deductible insurance beneficiaries, and those who were immunocompromised compared to immunocompetent. Among immunocompromised adults, RZV initiation was highest among those with HIV and primary immunodeficiencies. Of those who initiated RZV, 89.5% received both doses. RZV completion was highest among those who received the first dose at a pharmacy. Most enrollees (88.6%) who completed RZV vaccination did so within the recommended dosing schedule. CONCLUSIONS: RZV uptake was low in the two years since the CDC recommendation, and differed by demographic, healthcare access, and clinical characteristics. Initiation rates were higher among immunocompromised adults compared to immunocompetent adults, despite no CDC recommendation for vaccination in these groups during the study period. The CDC has since recommended RZV for immunocompromised individuals, and our findings may inform efforts to increase RZV uptake in individuals at higher risk of severe disease.

Acceptability and readiness to promote human papillomavirus vaccination at ages 9-10 years: a feasibility study among North Carolina clinics.

While 9-valent human papillomavirus (HPV) vaccination is approved by the US Food and Drug Administration for use in adolescents as young as age 9, providers typically recommend it at ages 11-12. Studies suggest that recommending HPV vaccination at 9 or 10 years of age could increase up-to-date vaccination by age 13, which could especially benefit rural populations with reduced access to primary health care and lower HPV vaccination coverage than urban areas. This study aimed to assess the feasibility of the age-9 recommendation of HPV vaccination in rural clinics. We conducted in-depth interviews with providers and staff from two primary care clinics in central North Carolina to understand attitudes toward recommending HPV vaccination to 9- and 10-year-olds. All interviewees agreed that HPV vaccination was important for cancer prevention and should be recommended before the onset of sexual activity, agreeing that HPV vaccination could be initiated before age 11 to improve timeliness and completion of the vaccination series. However, opinions were mixed on whether HPV vaccination should be initiated as young as 9 years old. Two key informants recruited from two university-affiliated clinics described their experiences recommending HPV vaccination to 9- and 10-year-olds, including a modified vaccination schedule that promotes HPV vaccination during routine well-child visits, prior to pubertal onset, and alongside other recommended adolescent vaccines. Age-9 recommendation and administration of HPV vaccination is possible with minimal changes to current clinical practices and could increase the convenience and acceptability of HPV vaccination in under-vaccinated settings.

Neural tube defects: Prevalence, mortality, and maternal characteristics in two departmental hospitals in the northwestern region of Nicaragua, 2006-2018.

BACKGROUND: Congenital anomalies are the fifth most common cause of neonatal mortality in Nicaragua, and neural tube defects (NTDs) are the most common of all cases of lethality associated with a birth defect. Prevalence and mortality estimates are needed to propose effective intervention strategies that prevent NTDs over time. METHODS: A cross-sectional study was carried out in northwestern Nicaragua from January 2006 to December 2018. All cases of NTDs (anencephaly, spina bifida, and encephalocele) were registered in hospital surveillance systems, and the medical histories of the mothers and newborns were reviewed. Prevalence was calculated by considering the number of live births and stillbirths older than 20 weeks of gestation with NTDs, divided by the total number of live births and stillbirths in each study year. Neonatal mortality rate (NMR) for NTD, and case fatality for spina bifida was calculated. RESULTS: Two hundred fifty cases of NTDs were identified from 178,498 deliveries (177,316 live births and 1,182 stillbirths). The prevalence of NTDs during this time period was 14.01 (95% CI: 12.27-15.74) per 10,000 births. The prevalence of spina bifida (n = 140), anencephaly (n = 97), and encephalocele (n = 13) was 7.84, (95% CI: 6.54-9.14), 5.43 (95% CI: 4.30-6.45), and 0.73 (95% CI: 0.33-1.12) per 10,000 births, respectively. Mothers with fetus or newborns affected with NTDs did not use folic acid prior to conception, and 11% experienced periods of hyperthermia during the first trimester of pregnancy. NMR for NTDs was 0.55 per 1.000 livebirths. Case fatality for all NTDs and for spina bifida were 55% and 18%, respectively. CONCLUSION: The prevalence and mortality of NTDs in the northwestern region of Nicaragua present peaks and troughs during the study period. Spina bifida was the most frequent type of NTD. We believe that these findings could be of use by health policy makers to strengthen the primary prevention of NTDs in the region through the monitoring of the food fortification policy and folic acid supplementation to women of childbearing age. Additional etiologic studies of NTDs should be considered to identify additional prevention measures.

Timing and genotype distribution of symptomatic and asymptomatic sapovirus infections and re-infections in a Nicaraguan birth cohort.

OBJECTIVES: To characterize the timing and genotype distribution of symptomatic and asymptomatic sapovirus infections and re-infections in a Nicaraguan birth cohort. METHODS: Infants (N = 444) were enrolled at 10-14 days of life and observed weekly until 2 years of age. Stool samples were collected for each acute gastroenteritis (AGE) episode, and routine stool samples were collected monthly. Stool samples were tested for sapovirus using RT-qPCR, and positive samples were genotyped. RESULTS: A total of 348 children completed 2 years of AGE weekly surveillance; 93 (26.7%) of them experienced sapovirus AGE. Most infections occurred after 5 months of age and mainly during the second year of life (62.4%, 58/93) and early in the rainy season. Sapovirus screening in all stools from a subset of 67 children who consistently provided samples showed sapovirus infections in 91 of 330 (27.6%) AGE episodes and in 39 of 1350 (2.9%) routine stools. In this subset, the median age at the first sapovirus AGE was 11.2 months (95% CI, 9.3-15.9 months); 38 of 67 (57%) children experienced re-infections, 19 symptomatic and 19 asymptomatic. On average, sapovirus re-infections were reported 7.2 months after symptomatic and 5.3 months after asymptomatic infections. Genogroup GI (64%, 69/108) was the most common detected. Sapovirus GI.1 was more frequently detected in AGE stool samples than in routine stool samples (47.2%, 43/91 vs. 25.6%, 10/39; p 0.005), and re-infection with the same genotype was uncommon. DISCUSSION: The first sapovirus infections occurred at approximately 11 months of age, whereas the median time to symptomatic re-infection was 7.2 months. Re-infections with the same sapovirus genotype were rare during 2 years of life suggesting genotype-specific protection after natural infection.

Epidemiology of pediatric astrovirus gastroenteritis in a Nicaraguan birth cohort.

Background: Astrovirus is a leading cause of acute gastroenteritis in children worldwide. However, few prospective studies have analyzed astrovirus in community-dwelling pediatric populations in low-and-middle-income countries. Methods: We assessed the incidence, risk factors, clinical characteristics, genotypes, viral coinfections and seasonality of astrovirus gastroenteritis in 443 healthy Nicaraguan children born in 2017-2018, followed for 36 months. Children were recruited from maternity hospitals and birth records in an economically-diverse neighborhood of León, the second-largest city in Nicaragua. Astrovirus-positive episodes and genotypes were identified from diarrheal specimens with reverse transcription quantitative polymerase chain reaction and Sanger sequencing. Results: Of 1708 total specimens tested, eighty children (18%) experienced at least 1 astrovirus episode, and 9 experienced repeat episodes, mostly during the rainy season (May-October). The incidence of astrovirus episodes was 7.8/100 child-years (95% CI: 6.2, 9.8). Genotype-specific incidence of astrovirus also exhibited seasonality. Median age of astrovirus episode onset was 16 months (IQR 9, 23). Initial astrovirus episodes were not associated with protection against future episodes during the age span studied. Astrovirus cases were exclusively breastfed for a shorter period than uninfected children, and the human milk oligosaccharide lacto-N-fucopentaose-I was more concentrated in mothers of these children. Home toilets appeared to protect against future astrovirus episodes (HR=0.19, 95% CI 0.04-0.91). Human astrovirus-5 episodes, comprising 15% of all typed episodes, were associated with longer diarrhea and more symptomatic rotavirus co-infections. Conclusion: Astrovirus was a common cause of gastroenteritis in this cohort, and future studies should clarify the role of astrovirus genotype in clinical infection severity.

Efficacy of Messenger RNA-1273 Against Severe Acute Respiratory Syndrome Coronavirus 2 Acquisition in Young Adults From March to December 2021.

Background: The efficacy of messenger RNA (mRNA)-1273 against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is not well defined, particularly among young adults. Methods: Adults aged 18-29 years with no known history of SARS-CoV-2 infection or prior vaccination for coronavirus disease 2019 (COVID-19) were recruited from 44 US sites from 24 March to 13 September 2021 and randomized 1:1 to immediate vaccination (receipt of 2 doses of mRNA-1273 vaccine at months 0 and 1) or the standard of care (receipt of COVID-19 vaccine). Randomized participants were followed up for SARS-CoV-2 infection measured by nasal swab testing and symptomatic COVID-19 measured by nasal swab testing plus symptom assessment and assessed for the primary efficacy outcome. A vaccine-declined observational group was also recruited from 16 June to 8 November 2021 and followed up for SARS-CoV-2 infection as specified for the randomized participants. Results: The study enrolled 1149 in the randomized arms and 311 in the vaccine-declined group and collected >122 000 nasal swab samples. Based on randomized participants, the efficacy of 2 doses of mRNA-1273 vaccine against SARS-CoV-2 infection was 52.6% (95% confidence interval, -14.1% to 80.3%), with the majority of infections due to the Delta variant. Vaccine efficacy against symptomatic COVID-19 was 71.0% (95% confidence interval, -9.5% to 92.3%). Precision was limited owing to curtailed study enrollment and off-study vaccination censoring. The incidence of SARS-CoV-2 infection in the vaccine-declined group was 1.8 times higher than in the standard-of-care group. Conclusions: mRNA-1273 vaccination reduced the incidence of SARS-CoV-2 infection from March to September 2021, but vaccination was only one factor influencing risk. Clinical Trials Registration: NCT04811664.