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 time distribution of astrovirus gastroenteritis in 443 healthy Nicaraguan children born in 2017 to 2018 who were followed for 36 months. Children were recruited from hospitals and birth records in an economically diverse neighborhood of León city. Astrovirus-positive episodes and genotypes were identified from stool with reverse transcription quantitative polymerase chain reaction and Sanger sequencing. Results: Of 1708 total specimens tested, 80 children (18%) experienced at least 1 astrovirus episode, and 9 experienced repeat episodes, mostly during the rainy season (May-October). Initial astrovirus episodes were not associated with a lowered risk against future episodes. In exploratory analyses, home toilets were associated with a lower risk of future astrovirus episodes (hazard ratio, 0.19; 95% CI, .04-.91). Human astrovirus 5 episodes, representing 15% of all typed episodes, were associated with longer diarrhea and more symptomatic rotavirus coinfections. Conclusions: Astrovirus was a common cause of gastroenteritis in this cohort, and future studies should clarify the role of astrovirus genotype in clinical infection severity.

Charting the impact of maternal antibodies and repeat exposures on sapovirus immunity in early childhood from a Nicaraguan birth cohort.

BACKGROUND: Sapovirus is an important cause of acute gastroenteritis in childhood. While vaccines against sapovirus may reduce gastroenteritis burden, a major challenge to their development is a lack of information about natural immunity. METHODS: We measured sapovirus-specific IgG in serum collected, between 2017 and 2020, of mothers soon after delivery and at 6 time points in Nicaraguan children until 3 years of age (n=112 dyads) using virus-like particles representing three sapovirus genotypes (GI.1, GI.2, GV.1). RESULTS: Sixteen (14.3%) of the 112 children experienced at least one sapovirus gastroenteritis episode, of which GI.1 was the most common genotype. Seroconversion to GI.1 and GI.2 was most common between 5 and 12 months of age, while seroconversion to GV.1 peaked at 18 to 24 months of age. All children who experienced sapovirus GI.1 gastroenteritis seroconverted and developed genotype-specific IgG. The impact of sapovirus exposure on population immunity was determined using antigenic cartography: newborns share their mothers' broadly binding IgG responses, which declined at 5 months of age and then increased as infants experienced natural sapovirus infections. CONCLUSION: By tracking humoral immunity to sapovirus over the first 3 years of life, this study provides important insights for the design and timing of future pediatric sapovirus vaccines.

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.

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.

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.

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.

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.

Rectovaginal Colonization with Serotypes of Group B Streptococci with Reduced Penicillin Susceptibility among Pregnant Women in León, Nicaragua.

Group B Streptococci (GBS) are important causes of neonatal sepsis and meningitis globally. To elucidate the potential benefits of maternal GBS vaccines, data is needed on the epidemiology of maternal GBS rectovaginal colonization, distribution of serotypes, and resistance to intrapartum antibiotic prophylaxis (IAP). We collected rectal and vaginal samples from 305 pregnant women in León, Nicaragua between 35 and 40 weeks gestation. Samples were cultured for GBS and confirmed using latex agglutination. GBS isolates underwent serotyping by quantitative polymerase chain reaction, and antimicrobial susceptibility testing by disk diffusion and microdilution following Clinical Laboratory Standard Institute guidelines. Sixty-three women (20.7%) were colonized with GBS in either the rectum or the vagina. Of 91 GBS isolates collected from positive cultures, most were serotypes II (28.6%), Ia (27.5%), and III (20.9%). Most GBS isolates (52.9%) were resistant to penicillin, the first-line prophylactic antibiotic. Penicillin resistance was highly correlated with resistance to vancomycin, ceftriaxone, and meropenem. The results of our study suggest that one-fifth of pregnant women in the urban area of León, Nicaragua are colonized with GBS and risk transmitting GBS to their offspring during labor. High resistance to commonly available antibiotics in the region suggests that prophylactic maternal GBS vaccination would be an effective alternative to IAP.

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 Nicaraguan population.

In a Nicaraguan population-based cohort, SARS-CoV-2 seroprevalence was 34%, with higher prevalence in children compared to adults. Having a seropositive household member was associated with a two-fold probability of individual seropositivity, suggesting a role for household transmission. Co-morbidities and preventive behaviors were not associated with SARS-CoV-2 seroprevalence.

Clinical Characteristics, Risk Factors, and Population Attributable Fraction for Campylobacteriosis in a Nicaraguan Birth Cohort.

Campylobacteriosis is an important contributor to the global burden of acute gastroenteritis (AGE). In Nicaragua, the burden, risk factors, and species diversity for infant campylobacteriosis are unknown. Between June 2017 and December 2018, we enrolled 444 infants from León, Nicaragua, in a population-based birth cohort, conducting weekly household AGE surveillance. First, we described clinical characteristics of symptomatic Campylobacter infections, and then compared clinical characteristics between Campylobacter jejuni/coli and non-jejuni/coli infections. Next, we conducted a nested case-control analysis to examine campylobacteriosis risk factors. Finally, we estimated the population attributable fraction of campylobacteriosis among infants experiencing AGE. Of 296 AGE episodes in the first year of life, Campylobacter was detected in 59 (20%), 39 were C. jejuni/coli, and 20 were non-jejuni/coli species, including the first report of Campylobacter vulpis infection in humans. Acute gastroenteritis symptoms associated with C. jejuni/coli lasted longer than those attributed to other Campylobacter species. In a conditional logistic regression model, chickens in the home (odds ratio [OR]: 3.8, 95% CI: 1.4-9.8), a prior AGE episode (OR: 3.3; 95% CI: 1.4-7.8), and poverty (OR: 0.4; 95% CI: 0.2-0.9) were independently associated with campylobacteriosis. Comparing 90 infants experiencing AGE with 90 healthy controls, 22.4% (95% CI: 11.2-32.1) of AGE episodes in the first year of life could be attributed to Campylobacter infection. Campylobacter infections contribute substantially to infant AGE in León, Nicaragua, with non-jejuni/coli species frequently detected. Reducing contact with poultry in the home and interventions to prevent all-cause AGE may reduce campylobacteriosis in this setting.

Risk Factors and Clinical Profile of Sapovirus-associated Acute Gastroenteritis in Early Childhood: A Nicaraguan Birth Cohort Study.

BACKGROUND: Sapovirus is increasingly recognized as an important cause of acute gastroenteritis (AGE) in children. We identified risk factors and characterized the clinical profile of sapovirus AGE in a birth cohort in León, Nicaragua. METHODS: We conducted a case-control study nested within a birth cohort (n = 444). Fieldworkers conducted weekly household AGE surveillance. AGE stools were tested for sapovirus by reverse transcriptase quantitative polymerase chain reaction. For each first sapovirus episode, we selected 2 healthy age-matched controls and estimated independent risk factors of sapovirus AGE using conditional logistic regression. We compared clinical characteristics of sapovirus AGE episodes with episodes associated with other etiologies and identified co-infections with other enteric pathogens. RESULTS: From June 2017 to July 2019, we identified 63 first sapovirus AGE episodes and selected 126 controls. Having contact with an individual with AGE symptoms and vaginal delivery were independent risk factors for sapovirus AGE. All cases experienced diarrhea, lasting a median 6 days; 23% experienced vomiting. Compared with children with AGE due to another etiology, sapovirus AGE was similar in severity, with less reported fever. Most cases experienced co-infections and were more likely than controls to be infected with diarrheagenic Escherichia coli or astrovirus. CONCLUSIONS: Sapovirus was a commonly identified AGE etiology in this Central American setting, and symptoms were similar to AGE associated with other etiologies. The association between vaginal delivery and sapovirus is a novel finding. Gut microbiome composition might mediate this relationship, or vaginal delivery might be a proxy for other risk factors. Further investigation into more specific biological mechanisms is warranted.

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.

Rectovaginal group B streptococcus colonization among pregnant women in Nicaragua: a systematic review and meta-analysis.

BACKGROUND: Maternal colonization with group B Streptococcus (GBS) is a predictor of neonatal sepsis. In Nicaragua, neonatal sepsis is a major cause of hospitalization, but it can be prevented with intrapartum antibiotic prophylaxis. We undertook this study to estimate the pooled prevalence of rectovaginal GBS colonization among pregnant women 35-40-week gestation in Nicaragua, and sensitivity of GBS isolates to various antibiotics. METHODS: We systematically searched electronic databases of peer-reviewed and unpublished literature using prespecified search terms. We included English- and Spanish-language studies of rectovaginal GBS colonization and/or antibiotic sensitivity of GBS isolates that followed internationally-recognized diagnostic standards, from various sites and years. Two reviewers independently abstracted data and assessed risk of study bias. We then meta-analyzed the pooled prevalence of rectovaginal GBS colonization and antibiotic sensitivity of GBS isolates. We performed subgroup analyses by geographic location, urbanicity, and study risk of bias. MAIN RESULTS: Prevalence of rectovaginal GBS colonization from 13 samples in 11 studies was 0.14 (95% CI: 0.09, 0.21). Effect size heterogeneity was identified between coastal (0.12 [95% CI: 0.07, 0.19]) and central study sites (0.23 [95% CI: 0.18, 0.28]), and between predominantly rural (0.06 [95% CI: 0.02, 0.10]) and urban (0.28 [95% CI: 0.19, 0.37]) samples of pregnant women. GBS sensitivity to penicillin, the first-line antibiotic for intrapartum prophylaxis, was 0.89 (95% CI: 0.71, 1.00) based on seven studies. CONCLUSIONS: Maternal GBS colonization was substantial in some study sites. Most GBS isolates are sensitive to recommended antibiotics, and intrapartum antibiotic prophylaxis may effectively prevent neonatal sepsis in Nicaragua.

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.