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BackgroundHome-based interventions have potential for improving early child development (ECD) in low-resource settings. The design of locally acceptable strategies requires an in-depth understanding of the household context. In this formative research study, we aimed to characterize the home play and learning environments of children 6–23 months of age from low-income households in peri-urban Lima, Peru.MethodsDrawing on the developmental niche framework, we used quantitative and qualitative methods to understand children’s physical and social settings, childcare practices, and caregiver perspectives. We conducted interviews, unstructured video-recorded observations, and spot-checks with 30 randomly selected caregiver-child dyads, 10 from each child age group of 6–11, 12–17, and 18–23 months of age, as well as key informant interviews with 12 daycare instructors. We analyzed the data for key trends and themes using Stata and ATLAS.ti and employed an adapted version of the Indicator of Parent-Child Interaction to evaluate the observations.ResultsChildren’s social settings were characterized by multi-generational homes and the presence of siblings and cousins as play partners. Access to books and complex hand-eye coordination toys (e.g., puzzles, building blocks) in the home was limited (30.0 and 40.0%, respectively). Caregivers generally demonstrated low or inconsistent levels of interaction with their children; they rarely communicated using descriptive language or introduced novel, stimulating activities during play. Reading and telling stories to children were uncommon, yet 93.3% of caregivers reported singing to children daily. On average, caregivers ascribed a high learning value to reading books and playing with electronic toys (rated 9.7 and 9.1 out of 10, respectively), and perceived playing with everyday objects in the home as less beneficial (rated 6.8/10). Daycare instructors reinforced the problems posed by limited caregiver-child interaction and supported the use of songs for promoting ECD.ConclusionsThe features of the home learning environments highlighted here indicate several opportunities for intervention development to improve ECD. These include encouraging caregivers to communicate with children using full sentences and enhancing the use of everyday objects as toys. There is also great potential for leveraging song and music to encourage responsive caregiver-child interactions within the home setting.

OBJECTIVES To inform next steps in pediatric diarrhea burden reduction by understanding the shifting enteropathogen landscape after rotavirus vaccine implementation. METHODS We conducted a case-control study of 1788 medically attended children younger than 5 years, with and without gastroenteritis, after universal rotavirus vaccine implementation in Peru. We tested case and control stools for 5 viruses, 19 bacteria, and parasites; calculated coinfection-adjusted attributable fractions (AFs) to determine pathogen-specific burdens; and evaluated pathogen-specific gastroenteritis severity using Clark and Vesikari scales. RESULTS Six pathogens were independently positively associated with gastroenteritis: norovirus genogroup II (GII) (AF 29.1, 95% confidence interval [CI]: 28.0–32.3), rotavirus (AF 8.9, 95% CI: 6.8–9.7), sapovirus (AF 6.3, 95% CI: 4.3–7.4), astrovirus (AF 2.8, 95% CI: 0.0–4.0); enterotoxigenic Escherichia coli heat stable and/or heat labile and heat stable (AF 2.4, 95% CI: 0.6–3.1), and Shigella spp. (AF 2.0, 95% CI: 0.4–2.2). Among typeable rotavirus cases, we most frequently identified partially heterotypic strain G12P[8] (54 of 81, 67%). Mean severity was significantly higher for norovirus GII–positive cases relative to norovirus GII–negative cases (Vesikari [12.7 vs 11.8; P < .001] and Clark [11.7 vs 11.4; P = .016]), and cases in the 6- to 12-month age range relative to cases in other age groups (Vesikari [12.7 vs 12.0; P = .0002] and Clark [12.0 vs 11.4; P = .0016]). CONCLUSIONS Norovirus is well recognized as the leading cause of pediatric gastroenteritis in settings with universal rotavirus vaccination. However, sapovirus is often overlooked. Both norovirus and sapovirus contribute significantly to the severe pediatric disease burden in this setting. Decision-makers should consider multivalent vaccine acquisition strategies to target multiple caliciviruses in similar countries after successful rotavirus vaccine implementation.

Background Substantial evidence exists surrounding the health risks of breast milk substitutes (BMS) in place of exclusive breastfeeding among infants < 6 months of age in resource-poor settings. Yet, mothers’ experiences of selecting and purchasing BMS brands have not been well studied to date. This qualitative study explored the factors influencing BMS purchasing practices, along with the consequences of those decisions, in peri-urban Lima, Peru. Methods We conducted in-depth interviews (IDIs) with 29 mothers who had begun mixed-feeding their infants during the first 6 months of life. Interviews explored participants’ reasons for initiating infant formula use and their experiences of selecting, purchasing, and providing BMS to their children. Audio recordings were transcribed, coded, and key themes and illustrative vignettes were identified. Results The primary reported reasons for initiating infant formula use included having received a recommendation for infant formula from a healthcare provider, concerns about an infant’s weight gain, and the perception of insufficient breast milk. Mothers tended to initially purchase the BMS brand that had been recommended by a doctor, which was often more expensive than the alternatives. The costs of BMS, which escalated as infants grew, often disrupted the household economy and generated significant stress. While some mothers identified alternatives allowing them to continue purchasing the same brand, others chose to switch to less expensive products. Several mothers began to feed their infants follow-on formula or commercial milk, despite their awareness that such practices were not recommended for infants under 6 months of age. The approval of family members and the absence of an infant’s immediate adverse reaction influenced mothers’ decisions to continue purchasing these products. Conclusions The high costs of BMS may deepen existing socio-economic vulnerabilities and generate new risks for infant health. The continued dedication of resources towards breastfeeding education and support is critical, and strategies would benefit from underscoring the long-term financial and health consequences of infant formula use, and from strengthening women’s self-efficacy to refuse to initiate infant formula when recommended. In addition, health providers should be trained in counseling to help women to relactate or return to exclusive breastfeeding after cessation.

Region-specific Helicobacter pylori subpopulations have been identified. It is proposed that the hspAmerind subpopulation is being displaced from the Americans by an hpEurope population following the conquest. Our study aimed to describe the genomes and methylomes of H. pylori isolates from distinct Peruvian communities: 23 strains collected from three groups of Native Americans (Asháninkas [ASHA, n = 9], Shimaas [SHIM, n = 5] from Amazonas, and Punos from the Andean highlands [PUNO, n = 9]) and 9 modern mestizos from Lima (LIM). Closed genomes and DNA modification calls were obtained using SMRT/PacBio sequencing. We performed evolutionary analyses and evaluated genomic/epigenomic differences among strain groups. We also evaluated human genome-wide data from 74 individuals from the selected Native communities (including the 23 H. pylori strains donors) to compare host and bacterial backgrounds. There were varying degrees of hspAmerind ancestry in all strains, ranging from 7% in LIM to 99% in SHIM. We identified three H. pylori subpopulations corresponding to each of the Native groups and a novel hspEuropePeru which evolved in the modern mestizos. The divergence of the indigenous H. pylori strains recapitulated the genetic structure of Native Americans. Phylogenetic profiling showed that Orthogroups in the indigenous strains seem to have evolved differentially toward epigenomic regulation and chromosome maintenance, whereas OGs in the modern mestizo (LIM) seem to have evolved toward virulence and adherence. The prevalence of cagA+/vacA s1i1m1 genotype was similar across populations (p = 0.32): 89% in ASHA, 67% in PUNO, 56% in LIM and 40% in SHIM. Both cagA and vacA sequences showed that LIM strains were genetically differentiated (p < 0.001) as compared to indigenous strains. We identified 642 R-M systems with 39% of the associated genes located in the core genome. We found 692 methylation motifs, including 254 population-specific sequences not previously described. In Peru, hspAmerind is not extinct, with traces found even in a heavily admixed mestizo population. Notably, our study identified three new hspAmerind subpopulations, one per Native group; and a new subpopulation among mestizos that we named hspEuropePeru. This subpopulation seems to have more virulence-related elements than hspAmerind. Purifying selection driven by variable host immune response may have shaped the evolution of Peruvian subpopulations, potentially impacting disease outcomes.

Background: Norovirus (NV) causes acute gastroenteritis in infants. Humoral and fecal immunoglobulin A (IgA) responses have been correlated with protection against NV; however, the role of breast milk IgA against NV infection and associated diarrhea is still unknown. This study aimed to evaluate the protective role of NV-specific IgA in breast milk. Methods: We analyzed 95 breast milk samples collected from mothers enrolled in a birth cohort study conducted in Peru during 2016–2017. Samples were collected before the first NV infection of infants and tested for total IgA and NV-specific IgA using virus-like particles (VLPs) that represented GII·4 variants and non-GII·4 genotypes. Norovirus infection in infants was assessed by testing their stool samples for NV via real-time PCR. Breast milk samples were grouped according to NV infection and diarrheal status of infants: NV positive with diarrhea (NV+D+, n=18); NV positive without diarrhea (NV+D-, n=37); and NV negative without diarrhea (NV-D-, n=40). The percent positivity and titer of NV-specific IgA (Log10) were compared among groups. Findings: Breast milk IgA had a high percent positivity against different NV VLPs, especially against GII (89–100%). Higher median titer of NV-specific IgA was observed in NV+D- when compared to the NV+D+ group against GII·4 Sydney (NV+D+:500 vs. NV+D-:100, p=0·05) and GI·1 (NV+D+:100 vs. NV+D-:50, p=0·01). Although the median titer of NV IgA against GI·9 was similar, NV+D- had higher distribution of titers when compared to NV+D+ group (NV+D-:100 [interquartile range (IQR):100–500] vs. NV+D+:100 [IQR:50–200], p=0·03). Interpretations: Breast milk IgA highly reacted to different NV VLPs. NV-specific IgA may protect infants from having NV-associated diarrhea, but not from NV infection, thus reducing NV symptoms. Funding Statement: National Institute of Allergy and Infectious Diseases, National Institute of Health: 1R01AI108695–01A1 and the Japan Society for the Promotion of Science (Fostering Joint International Research B): 19KK0241 Declaration of Interests: We declare that we have no conflicts of interest. Ethics Approval Statement: The mothers included in this study were selected from a larger birth cohort study carried out in Peru during 2016-2017. The birth cohort study was approved by the Institutional Review Boards of Asociacion Benefica PRISMA, Universidad Peruana Cayetano Heredia, Johns Hopkins University, University of California-San Francisco. Informed consent were obtained from the mothers or caretakers of the infants. The analysis of archived specimen was approved by the ethics committee of the Tohoku University, Graduate School of Medicine.

Feeding of infant formula using contaminated bottles may be an important transmission pathway of enteric pathogens during early life. Determinants of suboptimal bottle hygiene and the feasibility and acceptability of intervention strategies have not been well assessed. We evaluated the extent of bottle contamination, its contributing factors, and options for promoting improved bottle hygiene in a Peruvian shantytown. During Phase 1, we sampled from bottles and caregiver hands (n = 48) and processed for enumeration of total coliform and Escherichia coli colony-forming units. A semi-structured questionnaire captured bottle use and hygiene practices. Phase 2 involved the identification of candidate practices to recommend to caregivers. Phase 3 consisted of a behavioral trial in which 14 caregivers were educated about improved practices for bottle disinfection and later reported on their experiences implementing them. Fecal bacteria were detected in 43.8% of bottles sampled during Phase 1 and in 21.7% of hands. Caregivers overall did not use effective methods for disinfecting bottles, displayed misunderstandings surrounding hygienic practices, and few had ever discussed bottle hygiene with a health provider. Findings from the behavioral trial indicated that the improved practice of brushing the bottle with dish detergent for 30 seconds after every use is preferable to boiling the bottle for several minutes daily as caregivers reported that the brush was simple to use, efficient, and practical. The promotion of a bottle brush and detergent is a feasible and acceptable intervention strategy in peri-urban settings, and future research should evaluate its long-term effectiveness for reducing bottle contamination.

Antibiotic-resistant infections annually claim hundreds of thousands of lives worldwide. This problem is exacerbated by exchange of resistance genes between pathogens and benign microbes from diverse habitats. Mapping resistance gene dissemination between humans and their environment is a public health priority. Here we characterized the bacterial community structure and resistance exchange networks of hundreds of interconnected human faecal and environmental samples from two low-income Latin American communities. We found that resistomes across habitats are generally structured by bacterial phylogeny along ecological gradients, but identified key resistance genes that cross habitat boundaries and determined their association with mobile genetic elements. We also assessed the effectiveness of widely used excreta management strategies in reducing faecal bacteria and resistance genes in these settings representative of low- and middle-income countries. Our results lay the foundation for quantitative risk assessment and surveillance of resistance gene dissemination across interconnected habitats in settings representing over two-thirds of the world's population.

Background Bacillus Calmette–Guerin (BCG) scar formation is considered a visual marker of vaccination and cell-mediated immune response. This study characterized the association between pregnancy and birth characteristics with BCG scar formation. Study Design Pregnant women were enrolled prospectively. Infants were followed up for the first 6 months of life, and the diameter of the BCG scar was recorded. Marginal models were fitted to assess the association of BCG scar diameter with pregnancy and birth characteristics using linear regressions with generalized estimating equations. Results A total of 307 infants were enrolled, of whom 19.2% (59/307) were of low birth weight. Among those with known gestational age, 7.1% were preterm births (21/295). Overall, 98.7% (303/307) of infants developed a BCG scar. BCG scar trends in a tropical environment, such as the Amazon, differ from the trends evidenced in the capital of Peru. For every additional week of gestational age, the mean scar diameter increased by 0.1 mm (95% confidence interval [CI]: 0.02, 0.24; p = 0.017). Maternal illness during pregnancy impacted BCG scar size, as the infants of mothers who self-report fever had a smaller scar diameter (1 mm, 95% CI: 0.5, 1.8 mm; p = 0.001). Conclusion The immune reaction to the BCG vaccination is affected by gestational age at birth and systemic inflammatory episodes during pregnancy.

Background: More than one billion people worldwide live with a disability. Despite advances in recognising inequalities experienced by people with disabilities, barriers to services and stigmatisation still exist. The aims of this study were to explore: (1) perceptions and experiences of services specifically available to people with disabilities and their caregivers and (2) the perception of disability. Methods: In-depth interviews were conducted with 20 caregivers of persons with a disability and 14 key informants in two cities in Peru; Lima and Iquitos. The social-ecological model was used as a framework to analyse and present data, stratifying the key barriers and opportunities at each level. Results: At the individual level, interviewees reported a lack of support at the time of diagnosis, poor coping strategies, and communicated their desire for, and willingness to participate in support groups if they were established. On the community level, education and awareness were reportedly lacking and acts of discrimination and stigmatisation were common. Participants described opportunities for community-level campaigns to increase exposure and awareness of disability rights and inclusion. A dissatisfaction with government programmes was reported, as services were not available to everyone, in part due to geographical and socio-economic barriers. Conclusions: The main findings were the lack of emotional, informational, and tangible support available to caregivers of people with disabilities, often exacerbated by lower socio-economic status; a lack of transparency of care pathways available to people with disabilities; and a lack of visibility of people with disability in both Lima and Iquitos. Implications for Rehabilitation Support groups could offer additional support to caregivers of people with disabilities in Lima, mitigating existing gaps in services for people with disabilities, and their families. Education campaigns implemented on a community level could start to curb discrimination and stigmatisation of people with disabilities in Lima and Iquitos. A national census with inclusive language and methodology specifically designed to capture the percentage of the population currently living with a disability would give a real indication of what services are needed in Peru. The provision of clear, publically available routes of attention would assist caregivers and families to access services for people with disabilities.

This was the first birth cohort study with active surveillance of sapovirus infection in a developing country. High incidences of sapovirus infection and associated diarrhea during the first 2 years of life were reported. Sapovirus reinfection is common but rare with the same genotype., Background Sapovirus is one of the primary viral causes of acute gastroenteritis (AGE), especially where rotavirus vaccination has been implemented. The characteristics and impact of natural infection at the community level, however, have not been well documented. Methods Stool samples were analyzed from 100 children randomly selected from a community-based birth cohort study in Peru. All diarrheal and 1 nondiarrheal stools collected trimonthly from children up to age 2 years (n = 1669) were tested for sapovirus detection. Viral shedding duration was determined by testing additional weekly samples (n = 440) collected before and after a sapovirus-positive sample. Results The incidence of sapovirus infection in the first and second years of life was 4.3 and 11.1 per 100 child-months, respectively. By age 2 years, 82% of children had at least 1 sapovirus infection, and 64% had at least 1 sapovirus-associated diarrhea episode. The median shedding period was 18.5 days. In 112 of 175 infections, 14 genotypes from 4 genogroups (GI, GII, GIV, and GV) were determined. Among genogroups, GI were more frequently found in symptomatic infections than in asymptomatic infections (odds ratio, 3.1; 95% confidence interval, 1.3–7.4). Fifty-nine children had serial sapovirus infections, but only 3 had repeated infection of the same genotype. Conclusions Sapovirus was frequently detected in children with AGE at the community level during the first 2 years of life. Serial sapovirus infections by multiple genotypes in a child suggest genotype-specific immunity from each infection, which needs to be taken into account for vaccine development.

Background Childhood growth is a cornerstone of pediatric research. Statistical models need to consider individual trajectories to adequately describe growth outcomes. Specifically, well-defined longitudinal models are essential to characterize both population and subject-specific growth. Linear mixed-effect models with cubic regression splines can account for the nonlinearity of growth curves and provide reasonable estimators of population and subject-specific growth, velocity and acceleration. Methods We provide a stepwise approach that builds from simple to complex models, and account for the intrinsic complexity of the data. We start with standard cubic splines regression models and build up to a model that includes subject-specific random intercepts and slopes and residual autocorrelation. We then compared cubic regression splines vis-à-vis linear piecewise splines, and with varying number of knots and positions. Statistical code is provided to ensure reproducibility and improve dissemination of methods. Models are applied to longitudinal height measurements in a cohort of 215 Peruvian children followed from birth until their fourth year of life. Results Unexplained variability, as measured by the variance of the regression model, was reduced from 7.34 when using ordinary least squares to 0.81 (p

Aim To identify impairment in functional capacity associated with complicated and non-complicated diabetes using the 6-min walk distance test. Methods We enrolled 111 adults, aged ≥40 years, with Type 2 diabetes from a hospital facility and 150 healthy control subjects of similar age and sex from a community site in Lima, Peru. All participants completed a 6-min walk test. Results The mean age of the 261 participants was 58.3 years, and 43.3% were male. Among those with diabetes, 67 (60%) had non-complicated diabetes and 44 (40%) had complications such as peripheral neuropathy, retinopathy or nephropathy. The mean unadjusted 6-min walk distances were 376 m and 394 m in adults with and without diabetes complications, respectively, vs 469 m in control subjects (P

Population genetic studies have been used to understand the transmission of pathogens in humans and animals, especially the role of zoonotic infections and evolution and dispersal of virulent subtypes. In this study, we analysed the genetic diversity and population structure of Cryptosporidium meleagridis, the only known Cryptosporidium species that infects both avian and mammalian hosts and is responsible for approximately 10% of human cryptosporidiosis in some areas. A total of 62 C. meleagridis specimens from children, AIDS patients, and birds in Lima, Peru were characterised by sequence analysis of the ssrRNA gene and five minisatellite, microsatellite and polymorphic markers in chromosome 6, including the 60 kDa glycoprotein (gp60), 47 kDa glycoprotein (CP47), a serine repeat antigen (MSC6-5), retinitis pigmentosa GTPase regulator (RPGR) and thrombospondin protein 8 (TSP8). The multilocus sequence analysis identified concurrent infections with Cryptosporidium hominis in four AIDS patients and three children. Unique subtypes of C. meleagridis ranged from eight at the gp60 locus (gene diversity -Hd=0.651), three at the RPGR (Hd=0.556), three at the MSC6-5 locus (Hd=0.242), two at TSP8 (Hd=0.198), to one at CP47 (monomorphic), much lower than that of C. hominis in the same area. Intragenic linkage disequilibrium was strong and complete at all gene loci. Intergenic linkage disequilibrium was highly significant (P

Background. Human noroviruses are among the most common enteropathogens globally, and are a leading cause of infant diarrhea in developing countries. However, data measuring the impact of norovirus at the community level are sparse. Methods. We followed a birth cohort of children to estimate norovirus infection and diarrhea incidence in a Peruvian community. Stool samples from diarrheal episodes and randomly selected nondiarrheal samples were tested by polymerase chain reaction for norovirus genogroup and genotype. Excretion duration and rotavirus coinfection were evaluated in a subset of episodes. Results. Two hundred twenty and 189 children were followed to 1 and 2 years of age, respectively. By 1 year, 80% (95% confidence interval [CI], 75%–85%) experienced at least 1 norovirus infection and by 2 years, 71% (95% CI, 65%–77%) had at least 1 episode of norovirus-associated diarrhea. Genogroup II (GII) infections were 3 times more frequent than genogroup 1 (GI) infections. Eighteen genotypes were found; GII genotype 4 accounted for 41%. Median excretion duration was 34.5 days for GII vs 8.5 days for GI infection (P = .0006). Repeat infections by the same genogroup were common, but repeat infections by the same genotype were rare. Mean length-for-age z score at 12 months was lower among children with prior norovirus infection compared to uninfected children (coefficient: −0.33 [95% CI, −.65 to −.01]; P = .04); the effect persisted at 24 months. Conclusions. Norovirus infection occurs early in life and children experience serial infections with multiple genotypes, suggesting genotype-specific immunity. An effective vaccine would have a substantial impact on morbidity, but may need to target multiple genotypes.

Hospital infection control measures are crucial to tuberculosis (TB) control strategies within settings caring for human immunodeficiency virus (HIV)-positive patients, as these patients are at heightened risk of developing TB. Pyrazinamide (PZA) is a potent drug that effectively sterilizes persistent Mycobacterium tuberculosis bacilli. However, PZA resistance associated with mutations in the nicotinamidase/pyrazinamidase coding gene, pncA, is increasing. A total of 794 patient isolates obtained from four sites in Lima, Peru, underwent spoligotyping and drug resistance testing. In one of these sites, the HIV unit of Hospital Dos de Mayo (HDM), an isolation ward for HIV/TB coinfected patients opened during the study as an infection control intervention: circulating genotypes and drug resistance pre- and postintervention were compared. All other sites cared for HIV-negative outpatients: genotypes and drug resistance rates from these sites were compared with those from HDM. HDM patients showed high concordance between multidrug resistance, PZA resistance according to the Wayne method, the two most common genotypes (spoligotype international type [SIT] 42 of the Latino American-Mediterranean (LAM)-9 clade and SIT 53 of the T1 clade), and the two most common pncA mutations (G145A and A403C). These associations were absent among community isolates. The infection control intervention was associated with 58-92% reductions in TB caused by SIT 42 or SIT 53 genotypes (odds ratio [OR] = 0.420, P = 0.003); multidrug-resistant TB (OR = 0.349, P < 0.001); and PZA-resistant TB (OR = 0.076, P < 0.001). In conclusion, pncA mutation typing, with resistance testing and spoligotyping, was useful in identifying a nosocomial TB outbreak and demonstrating its resolution after implementation of infection control measures.

Human sapovirus has been shown to be one of the most important etiologies in pediatric patients with acute diarrhea. However, very limited data are available about the causative roles and epidemiology of sapovirus in community settings. A nested matched case-control study within a birth cohort study of acute diarrhea in a peri-urban community in Peru from 2007 to 2010 was conducted to investigate the attributable fraction (AF) and genetic diversity of sapovirus. By quantitative reverse transcription–real-time PCR (qPCR) sapovirus was detected in 12.4% (37/299) of diarrheal and 5.7% (17/300) of nondiarrheal stools ( P = 0.004). The sapovirus AF (7.1%) was higher in the second year (13.2%) than in the first year (1.4%) of life of children. Ten known genotypes and one novel cluster ( n = 5) within four genogroups (GI, GII, GIV, and GV) were identified by phylogenetic analysis of a partial VP1 gene. Further sequence analysis of the full VP1 gene revealed a possible novel genotype, tentatively named GII.8. Notably, symptomatic reinfections with different genotypes within the same ( n = 3) or different ( n = 5) genogroups were observed in eight children. Sapovirus exhibited a high attributable burden for acute gastroenteritis, especially in the second year of life, of children in a Peruvian community. Further large-scale studies are needed to understand better the global burden, genetic diversity, and repeated infections of sapovirus.

Beta-defensins are a family of multifunctional genes with roles in defense against pathogens, reproduction, and pigmentation. In humans, six beta-defensin genes are clustered in a repeated region which is copy-number variable (CNV) as a block, with a diploid copy number between 1 and 12. The role in host defense makes the evolutionary history of this CNV particularly interesting, because morbidity due to infectious disease is likely to have been an important selective force in human evolution, and to have varied between geographical locations. Here, we show CNV of the beta-defensin region in chimpanzees, and identify a beta-defensin block in the human lineage that contains rapidly evolving noncoding regulatory sequences. We also show that variation at one of these rapidly evolving sequences affects expression levels and cytokine responsiveness of DEFB103, a key inhibitor of influenza virus fusion at the cell surface. A worldwide analysis of beta-defensin CNV in 67 populations shows an unusually high frequency of high-DEFB103-expressing copies in East Asia, the geographical origin of historical and modern influenza epidemics, possibly as a result of selection for increased resistance to influenza in this region. Hum Mutat 32:743–750, 2011. © 2011 Wiley-Liss, Inc.

and is a major impediment to the management of childhood diseases in developing coun- tries such as Peru. Although resistance in pathogenic organ- isms poses a distinct clinical challenge, commensal bacteria may play a crucial role in the spread of resistance within a community 3 by acting as a major reservoir for resistance genes. 4 Exposure of commensals such as Escherichia coli and Enterococcus faecium to antibiotics increases the car- riage levels of resistant organisms and, if plasmid-mediated, resistance might be transmitted to a more virulent acquired organism. 5 Abstract. Few studies have examined the influence of individual-, household-, and community-scale risk factors on carriage of resistant commensal bacteria. We determined children's medical, agricultural, and environmental exposures by household, pharmacy, and health facility surveys and Escherichia coli cultures of children, mothers' hands, household animals, and market chickens in Peru. Among 522 children with a positive stool culture, by log-binomial regression, using "any antibiotic" and 1-14 (versus 0) sulfa doses in the past 3 months increased children's risk, respectively, for ampicil- lin- and sulfamethoxazole-resistant E. coli carriage ( P = 0.01-0.02). Each household member taking "any antibiotic" increased children's risk for sulfamethoxazole- and multidrug-resistant E. coli carriage ( P < 0.0001). Residence in a zone where a larger proportion of households served home-raised chicken (as contrasted with intensively antibiotic-raised market chicken) protected against carrying E. coli resistant to all drugs ( P = 0.0004-0.04). Environmental contamination with drug-resistant bacteria appeared to significantly contribute to children's carriage of antibiotic-resistant E. coli .