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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. An analysis of bacterial community structure and antibiotic resistance gene content of interconnected human faecal and environmental samples from two low-income communities in Latin America was carried out using a combination of functional metagenomics, 16S sequencing and shotgun sequencing; resistomes across habitats are generally structured along ecological gradients, but key resistance genes can cross these boundaries, and the authors assessed the usefulness of excreta management protocols in the prevention of resistance gene dissemination. Inadequate sanitation promotes transmission of antimicrobial resistance Mapping the distribution and dissemination of antibiotic resistance genes is a public health priority. Gautam Dantas and colleagues have characterized the bacterial community structure and resistance gene exchange networks from two low-income Latin American communities — a rural village of subsistence farmers 35 km south of San Salvador, El Salvador and a shanty town in the desert hills about 15 km southwest of Lima, Peru. Using functional genomics and whole-metagenome sequencing of hundreds of interconnected human faecal and environmental samples, the authors find that resistomes across habitats are generally structured by bacterial phylogeny along ecological gradients, but that key resistance genes can cross these boundaries. They also assess the usefulness of excreta management protocols in the prevention of resistance gene dissemination. Collectively, this work lays the foundation for quantitative risk assessment and surveillance of antibiotic resistance gene transmission across diverse environments.

To assess the extent of arsenic contamination of groundwater and surface water in Peru and, to evaluate the accuracy of the Arsenic Econo-Quick(™) (EQ) kit for measuring water arsenic concentrations in the field. Water samples were collected from 151 water sources in 12 districts of Peru, and arsenic concentrations were measured in the laboratory using inductively-coupled plasma mass spectrometry. The EQ field kit was validated by comparing a subset of 139 water samples analysed by laboratory measurements and the EQ kit. In 86% (96/111) of the groundwater samples, arsenic exceeded the 10 µg/l arsenic concentration guideline given by the World Health Organization (WHO) for drinking water. In 56% (62/111) of the samples, it exceeded the Bangladeshi threshold of 50 µg/l; the mean concentration being 54.5 µg/l (range: 0.1-93.1). In the Juliaca and Caracoto districts, in 96% (27/28) of groundwater samples arsenic was above the WHO guideline; and in water samples collected from the section of the Rímac river running through Lima, all had arsenic concentrations exceeding the WHO limit. When validated against laboratory values, the EQ kit correctly identified arsenic contamination relative to the guideline in 95% (106/111) of groundwater and in 68% (19/28) of surface water samples. In several districts of Peru, drinking water shows widespread arsenic contamination, exceeding the WHO arsenic guideline. This poses a public health threat requiring further investigation and action. For groundwater samples, the EQ kit performed well relative to the WHO arsenic limit and therefore could provide a vital tool for water arsenic surveillance.

While South Americans are underrepresented in human genomic diversity studies, Brazil has been a classical model for population genetics studies on admixture. We present the results of the EPIGEN Brazil Initiative, the most comprehensive up-to-date genomic analysis of any Latin-American population. A population-based genome-wide analysis of 6,487 individuals was performed in the context of worldwide genomic diversity to elucidate how ancestry, kinship, and inbreeding interact in three populations with different histories from the Northeast (African ancestry: 50%), Southeast, and South (both with European ancestry >70%) of Brazil. We showed that ancestry-positive assortative mating permeated Brazilian history. We traced European ancestry in the Southeast/South to a wider European/Middle Eastern region with respect to the Northeast, where ancestry seems restricted to Iberia. By developing an approximate Bayesian computation framework, we infer more recent European immigration to the Southeast/South than to the Northeast. Also, the observed low Native-American ancestry (6–8%) was mostly introduced in different regions of Brazil soon after the European Conquest. We broadened our understanding of the African diaspora, the major destination of which was Brazil, by revealing that Brazilians display two within-Africa ancestry components: one associated with non-Bantu/western Africans (more evident in the Northeast and African Americans) and one associated with Bantu/eastern Africans (more present in the Southeast/South). Furthermore, the whole-genome analysis of 30 individuals (42-fold deep coverage) shows that continental admixture rather than local post-Columbian history is the main and complex determinant of the individual amount of deleterious genotypes.

Background. Human noroviruses are among the most common enteropathogens globally, and are a leading cuae 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.

ObjectivesTo describe and quantify the dengue-related knowledge, attitudes and practices of residents in an urban shantytown in Lima, Peru.Design/settingA cross-sectional survey of adults between 18 and 80 years living in approximately 120 blocks in Oasis, an urban shantytown situated in the low-to-middle income district of Villa El Salvador in Southern Lima. The survey was adapted from an existing survey previously used in Iquitos, Peru, and included questions relating to knowledge of dengue symptoms, transmission, prevention and current mosquito control practices.ParticipantsA total of 240 surveys were completed with 80% of respondents being female and approximately 50% of all respondents describing themselves as housewives.ResultsAlthough 97.9% of respondents had heard of dengue, only 6.2% of people knew someone who had experienced the disease. Approximately half (54.2%) of the respondents knew dengue was transmitted by mosquitoes and 51.7% were able to identify fever and one other correct symptom of dengue. Female sex was significantly associated with greater symptom knowledge (OR 2.22, 95% CI 1.08 to 4.72) and prevention knowledge (OR 2.12, 95% CI 1.06 to 4.21). Past or current higher education attendance was significantly associated with symptom knowledge (OR 2.56, 95% CI 1.25 to 5.44) and transmission knowledge (OR 3.46, 95% CI 1.69 to 7.57). Knowledge of dengue was not significantly associated with carrying out practices to control mosquitoes (OR 1.76, 95% CI 0.87 to 3.54).ConclusionsThis population demonstrated baseline dengue knowledge. However, this was incomplete and substantially less when compared with endemic areas. Given the sporadic nature of dengue transmission in Lima, it is not surprising that knowledge of the disease was not associated with carrying out practices to reduce mosquitoes. However, as dengue transmission in Lima is likely to increase, understanding how best to improve public knowledge of the disease and how to translate this into appropriate community action will be a key public health consideration.

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.

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. 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. 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. 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 Home-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. Methods Drawing 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. Results Children’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. Conclusions The 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.

Blood malignancies arise from the dysregulation of haematopoiesis. The type of blood cell and the specific order of oncogenic events initiating abnormal growth ultimately determine the cancer subtype and subsequent clinical outcome. HOXA9 plays an important role in acute myeloid leukaemia (AML) prognosis by promoting blood cell expansion and altering differentiation; however, the function of HOXA9 in other blood malignancies is still unclear. Here, we highlight the biological switch and prognosis marker properties of HOXA9 in AML and chronic myeloproliferative neoplasms (MPN). First, we establish the ability of HOXA9 to stratify AML patients with distinct cellular and clinical outcomes. Then, through the use of a computational network model of MPN, we show that the self-activation of HOXA9 and its relationship to JAK2 and TET2 can explain the branching progression of JAK2/TET2 mutant MPN patients towards divergent clinical characteristics. Finally, we predict a connection between the RUNX1 and MYB genes and a suppressive role for the NOTCH pathway in MPN diseases. HOXA9 plays an important role in acute myeloid leukaemia (AML), but its relevance for other blood malignancies is unclear. Here, the authors show that HOXA9 has a binary switch function that can clinically stratify AML patients, and model how the interactions with JAK2, TET2 and NOTCH impact myeloproliferative neoplasms.

Genes present in only certain strains of a bacterial species can strongly affect cellular phenotypes and evolutionary potentials. One segment that seemed particularly rich in strain-specific genes was found by comparing the first two sequenced Helicobacter pylori genomes (strains 26695 and J99) and was named a \"plasticity zone\". We studied the nature and evolution of plasticity zones by sequencing them in five more Helicobacter strains, determining their locations in additional strains, and identifying them in recently released genome sequences. They occurred as discrete units, inserted at numerous chromosomal sites, and were usually flanked by direct repeats of 5'AAGAATG, a sequence generally also present in one copy at unoccupied sites in other strains. This showed that plasticity zones are transposable elements, to be called TnPZs. Each full length TnPZ contained a cluster of type IV protein secretion genes (tfs3), a tyrosine recombinase family gene (\"xerT\"), and a large (>or=2800 codon) orf encoding a protein with helicase and DNA methylase domains, plus additional orfs with no homology to genes of known function. Several TnPZ types were found that differed in gene arrangement or DNA sequence. Our analysis also indicated that the first-identified plasticity zones (in strains 26695 and J99) are complex mosaics of TnPZ remnants, formed by multiple TnPZ insertions, and spontaneous and transposable element mediated deletions. Tests using laboratory-generated deletions showed that TnPZs are not essential for viability, but identified one TnPZ that contributed quantitatively to bacterial growth during mouse infection and another that affected synthesis of proinflammatory cytokines in cell culture. We propose that plasticity zone genes are contained in conjugative transposons (TnPZs) or remnants of them, that TnPZ insertion is mediated by XerT recombinase, and that some TnPZ genes affect bacterial phenotypes and fitness.