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Abstract Background Antigen detection in Taenia solium cysticercosis confirms viable infection in the intermediate host (either pig or human). The reference B158/B60 monoclonal antibody (mAb)-based Ag-enzyme-linked immunosorbent assay (ELISA) has acceptable levels of sensitivity and specificity in human neurocysticercosis with multiple brain cysts, although its sensitivity is lower in cases with single brain cysts, whereas in porcine cysticercosis the assay specificity is affected by its frequent cross-reaction with Taenia hydatigena, another common cestode found in pigs. Our group has produced 21 anti-T. solium mAbs reacting against antigens of the whole cyst, vesicular fluid, and secretory/excretory products, identifying TsW8/TsW5 as the most promising pair of mAbs for an Ag-ELISA. Methods We report the use of the TsW8/TsW5 Ag-ELISA to measure cysticercus antigen levels [expressed as optical density (OD) values] in two panels of sera collected from day 0 (baseline) to day 90 postinfection (PI) from pigs experimentally infected with T. solium (n = 26) and T. hydatigena (n = 12). At baseline and on days 28 and 90 PI, we used Bland–Altman (BA) analysis and Lin’s concordance correlation coefficients (CCC) to determine the concordance between the TsW8/TsW5 and the B158/B60 Ag-ELISA. Results The TsW8/TsW5 Ag-ELISA was able to efficiently measure circulating antigen levels in T. solium-infected pigs, similar to that obtained with the B158/B60 Ag-ELISA. Almost all paired log-OD differences between assays were within the limits of agreement (LoA) in the BA analysis at baseline and on days 28 and 90 PI (92.3%, 100%, and 100%, respectively), and a high concordance of log-ODs between assays was also found (Lin’s CCC: 0.69, 0.92, and 0.96, respectively, all P

Summary:. For gender-diverse individuals assigned male at birth, postpubertal estrogen and testosterone-lowering therapies alone are often inadequate to reverse the testosterone-related facial characteristics projecting a male sex identity. Facial feminization surgery significantly improves quality-of-life outcomes for gender-diverse patients by relieving this gender incongruence of the face. Because the shape of the forehead is so radically different between men and women, feminization of this area is critical for many individuals. Several techniques are typically used in combination, including hairline advancement, browlift, burring of the supraorbital rims, frontal bone contouring, and anterior table setback. This report describes the use of fat grafting as an adjuvant technique to forehead contouring as means to avoid frontal bone osteotomy, which carries a higher complication profile and often requires hardware placement.

Not available.

Abstract There is still incomplete knowledge of which Mycobacterium tuberculosis (Mtb) antigens can trigger distinct T cell responses at different stages of infection. Here, a proteome-wide screen of 20,610 Mtb-derived peptides in 21 patients mid-treatment for active tuberculosis (ATB) reveals IFNγ-specific T cell responses against 137 unique epitopes. Of these, 16% are recognized by two or more participants and predominantly derived from cell wall and cell processes antigens. There is differential recognition of antigens, including TB vaccine candidate antigens, between ATB participants and interferon-gamma release assay (IGRA + /−) individuals. We developed an ATB-specific peptide pool (ATB116) consisting of epitopes exclusively recognized by ATB participants. This pool can distinguish patients with pulmonary ATB from IGRA + /− individuals from various geographical locations, with a sensitivity of over 60% and a specificity exceeding 80%. This proteome-wide screen of T cell reactivity identified infection stage-specific epitopes and antigens for potential use in diagnostics and measuring Mtb-specific immune responses.

ABSTRACTChildren living in low-resource settings are frequently gut-colonized with multidrug-resistant bacteria. We explored whether breastfeeding may protect against children’s incident gut colonization with extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-Ec) and Klebsiella, Enterobacter, or Citrobacter spp. (ESBL-KEC). We screened 937 monthly stool samples collected from 112 children aged 1–16 months during a 2016–19 prospective cohort study of enteric infections in peri-urban Lima. We used 52,816 daily surveys to examine how exposures to breastfeeding in the 30 days prior to a stool sample were associated with children’s risks of incident gut-colonization, controlling for antibiotic use and other covariates. We sequenced 78 ESBL-Ec from 47 children to explore their diversity. Gut-colonization with ESBL-Ec was increasingly prevalent as children aged, approaching 75% by 16 months, while ESBL-KEC prevalence fluctuated between 18% and 36%. Through 6 months of age, exclusively providing human milk in the 30 days prior to a stool sample did not reduce children’s risk of incident gut-colonization with ESBL-Ec or ESBL-KEC. From 6 to 16 months of age, every 3 additional days of breastfeeding in the prior 30 days was associated with 6% lower risk of incident ESBL-Ec gut-colonization (95% CI: 0.90, 0.98, p = .003). No effects were observed on incident ESBL-KEC colonization. We detected highly diverse ESBL-Ec among children and few differences between children who were predominantly breastfed (mean age: 4.1 months) versus older children (10.8 months). Continued breastfeeding after 6 months conferred protection against children’s incident gut colonization with ESBL-Ec in this setting. Policies supporting continued breastfeeding should be considered in efforts to combat antibiotic resistance.

Abstract Background Taenia solium is a parasite of public health concern, causing human taeniasis and cysticercosis. Two main genotypes have been identified: Asian and African-American. Although characterizing T. solium genotypes is crucial to understanding the genetic epidemiology of its diseases, not much is known about the differences between T. solium mitochondrial genomes from different genotypes. Also, little is known about whether genotypes are further subdivided. Therefore, this study aimed to identify a set of point mutations distributed throughout the T. solium mitochondrial genome that differentiate the African-American from the Asian genotype. Another objective was to identify whether T. solium main genotypes are further stratified. Methods One Mexican and two Peruvian T. solium mitochondrial genomes were assembled using reads available in the NCBI Sequence Read Archive and the reference genome from China as a template. Mutations with respect to the Chinese reference were identified by multiple genome alignment. Jensen–Shannon and Grantham scores were computed for mutations in protein-coding genes to evaluate whether they affected protein function. Phylogenies by Bayesian inference and haplotype networks were constructed using cytochrome c oxidase subunit 1 and cytochrome b from these genomes and other isolates to infer phylogeographical relationships. Results A set of 31 novel non-synonymous point mutations present in all genomes of the African-American genotype were identified. These mutations were distributed across the mitochondrial genome, differentiating the African-American from the Asian genotype. All occurred in non-conserved protein positions. Furthermore, the analysis suggested a stratification of the African-American genotypes into an East African and a West African sublineage. Conclusions A novel set of 31 non-synonymous mutations differentiating the main T. solium genotypes was identified. None of these seem to be causing differences in mitochondrial protein function between parasites of the two genotypes. Furthermore, two sublineages within the African-American genotype are proposed for the first time. The presence of the East African sublineage in the Americas suggests an underestimated connection between East African and Latin American countries that might have arisen in the major slave trade between Portuguese Mozambique and the Americas. The results obtained here help to complete the molecular epidemiology of the parasite. Graphical Abstract

BackgroundEnterotoxigenic E. coli (ETEC) is a leading cause of diarrheal morbidity and mortality in children, although the data on disease burden, epidemiology, and impact on health at the community level are limited.MethodsIn a longitudinal birth cohort study of 345 children followed until 24 months of age in Lima, Peru, we measured ETEC burden in diarrheal and non-diarrheal samples using quantitative PCR (LT, STh, and STp toxin genes), studied epidemiology and measured anthropometry in children.ResultsAbout 70% of children suffered from one or more ETEC diarrhea episodes. Overall, the ETEC incidence rate (IR) was 73 per 100 child-years. ETEC infections began early after birth causing 10% (8.9–11.1) ETEC-attributable diarrheal burden at the population level (PAF) in neonates and most of the infections (58%) were attributed to ST-ETEC [PAF 7.9% (1.9–13.5)] and LT + ST-ETEC (29%) of which all the episodes were associated with diarrhea. ETEC infections increased with age, peaking at 17% PAF (4.6–27.7%; p = 0.026) at 21 to 24 months. ST-ETEC was the most prevalent type (IR 32.1) with frequent serial infections in a child. The common colonization factors in ETEC diarrhea cases were CFA/I, CS12, CS21, CS3, and CS6, while in asymptomatic ETEC cases were CS12, CS6 and CS21. Only few (5.7%) children had repeated infections with the same combination of ETEC toxin(s) and CFs, suggested genotype-specific immunity from each infection. For an average ETEC diarrhea episode of 5 days, reductions of 0.060 weight-for-length z-score (0.007 to 0.114; p = 0.027) and 0.061 weight-for-age z-score (0.015 to 0.108; p = 0.009) were noted in the following 30 days.ConclusionThis study showed that ETEC is a significant pathogen in Peruvian children who experience serial infections with multiple age-specific pathotypes, resulting in transitory growth impairment.

Abstract Helminth/tuberculosis (TB)-coinfection can reduce cell-mediated immunity against Mycobacterium tuberculosis (Mtb) and increase disease severity, although the effects are highly helminth species dependent. Mtb have long been ranked as the number one single infectious agent claiming the most lives. The only licensed vaccine for TB (BCG) offers highly variable protection against TB, and almost no protection against transmission of Mtb. In recent few years the identification of naturally occurring antibodies in humans that are protective during Mtb infection has reignited the interest in adaptive humoral immunity against TB and its possible implementation in novel TB vaccine design. The effects of helminth/TB coinfection on the humoral response against Mtb during active pulmonary TB are however still unclear, and specifically the effect by globally prevalent helminth species such as Ascaris lumbricoides, Strongyloides stercoralis, Ancylostoma duodenale, Trichuris trichiura. Plasma samples from smear positive TB patients were used to measure both total and Mtb-specific antibody responses in a Peruvian endemic setting where these helminths are dominating. Mtb-specific antibodies were detected by a novel approach coating ELISA-plates with a Mtb cell-membrane fraction (CDC1551) that contains a broad range of Mtb surface proteins. Compared to controls without helminths or TB, helminth/TB coinfected patients had high levels of Mtb-specific IgG (including an IgG1 and IgG2 subclass response) and IgM, which were similarly increased in TB patients without helminth infection. These data, indicate that helminth/TB coinfected have a sustained humoral response against Mtb at the level of active TB only. More studies on the species-specific impact of helminths on the adaptive humoral response against Mtb using a larger sample size, and in relation to TB disease severity, are needed.

Background The long-term impact of elevated blood pressure on mortality outcomes has been recently revisited due to proposed changes in cut-offs for hypertension. This study aimed at assessing the association between high blood pressure levels and 10-year mortality using the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC-7) and the American College of Cardiology and the American Heart Association (ACC/AHA) 2017 blood pressure guidelines. Methods Data analysis of the PERU MIGRANT Study, a prospective ongoing cohort, was used. The outcome of interest was 10-year all-cause mortality, and exposures were blood pressure categories according to the JNC-7 and ACC/AHA 2017 guidelines. Log-rank test, Kaplan-Meier and Cox regression models were used to assess the associations of interest controlling for confounders. Hazard ratios (HR) and 95% confidence intervals (95% CI) were estimated. Results A total of 976 records, mean age of 60.4 (SD: 11.4), 513 (52.6%) women, were analyzed. Hypertension prevalence at baseline almost doubled from 16.0% (95% CI 13.7%–18.4%) to 31.3% (95% CI 28.4%–34.3%), using the JNC-7 and ACC/AHA 2017 definitions, respectively. Sixty-three (6.4%) participants died during the 10-year follow-up, equating to a mortality rate of 3.6 (95% CI 2.4–4.7) per 1000 person-years. Using JNC-7, and compared to those with normal blood pressure, those with pre-hypertension and hypertension had 2.1-fold and 5.1-fold increased risk of death, respectively. Similar mortality effect sizes were estimated using ACC/AHA 2017 for stage-1 and stage-2 hypertension. Conclusions Blood pressure levels under two different definitions increased the risk of 10-year all-cause mortality. Hypertension prevalence doubled using ACC/AHA 2017 compared to JNC-7. The choice of blood pressure cut-offs to classify hypertension categories need to be balanced against the patients benefit and the capacities of the health system to adequately handle a large proportion of new patients.

Objetivo. Explorar la viabilidad de desarrollar un modelo de neurocisticercosis (NCC) de oveja mediante infección intracraneal de oncosferas de T. solium. Materiales y métodos. Se realizó un modelo de infección experimental de NCC en ovejas. Se inocularon aproximadamente 10 posoncósferas de T. solium cultivadas previamente por 30 días por vía intracraneal en diez ovejas. Las oncósferas, en 0,1 mL de solución salina fisiológica, se inyectaron en el lóbulo parietal a través de una aguja de calibre 18. Resultados. Después de tres meses, en dos ovejas se encontraron granulomas y en una tercera identificó un quiste de 5 mm de diámetro en el ventrículo lateral derecho y la evaluación histológica confirmó que el quiste corresponde a una larva de T. solium. También se utilizó inmunohistoquímica con anticuerpos monoclonales dirigidos contra componentes de membrana y antígenos excretorios/secretorios del quiste de T. solium para confirmar la etiología de los granulomas encontrados. Uno de ellos mostro reactividad ante los anticuerpos monoclonales utilizados, confirmando así que se trató de un cisticerco Conclusión. Este experimento es la prueba de concepto de que es posible infectar ovejas con cisticercosis por inoculación intracraneal.

Neurocysticercosis (NCC) is the most common parasitic disease affecting the nervous system and is a leading cause of acquired epilepsy worldwide, as well as cognitive impairment, especially affecting memory. The aim of this study was to evaluate the effect of NCC on spatial working memory and its correlation with hippocampal neuronal density, in a rat model of NCC. This experimental study was conducted on female (n = 60) and male (n = 73) Holtzman rats. NCC was induced by intracranial inoculation of T. solium oncospheres in 14 day-old-rats. Spatial working memory was assessed using the T-maze test at 3, 6, 9, and 12 months post-inoculation, and sensorimotor evaluation was performed at 12 months post-inoculation. Hippocampal neuronal density was evaluated by immunostaining of NeuN-positive cells of the CA1 region. Of the rats inoculated with T. solium oncospheres, 87.2% (82/94) developed NCC. The study showed a significant decline in spatial working memory over a 1-year follow-up period in rats experimentally infected with NCC. Males showed an early decline that started at 3 months, while females demonstrated it at 9 months. Additionally, a decrease in neuronal density was observed in the hippocampus of NCC-infected rats, with a more significant reduction in rats with cysts in the hippocampus than in rats with cysts in other brain areas and control rats. This rat model of NCC provides valuable support for the relationship between neurocysticercosis and spatial working memory deficits. Further investigations are required to determine the mechanisms involved in cognitive impairment and establish the basis for future treatments.

Abstract PDE4B (phosphodiesterase‐4B) has an important role in cancer and in pharmacology of some disorders, such as inflammatory diseases. Remarkably in Native Americans, PDE4B variants are associated with acute lymphoblastic leukemia (ALL) relapse, as this gene modulates sensitivity of glucocorticoids used in ALL chemotherapy. PDE4B allele rs6683977.G, associated with genomic regions of Native American origin in US‐Hispanics (admixed among Native Americans, Europeans, and Africans), increases ALL relapse risk, contributing to an association between Native American ancestry and ALL relapse that disappeared with an extra‐phase of chemotherapy. This result insinuates that indigenous populations along the Americas may have high frequencies of rs6683977.G, but this has never been corroborated. We studied ancestry and PDE4B diversity in 951 healthy individuals from nine Latin American populations. In non‐admixed Native American populations rs6683977.G has frequencies greater than 90%, is in linkage disequilibrium with other ALL relapse associated and regulatory variants in PDE4B‐intron‐7, conforming haplotypes showing their highest worldwide frequencies in Native Americans (>0.82). Our findings inform the discussion on the pertinence of an extra‐phase of chemotherapy in Native American populations, and exemplifies how knowledge generated in US‐Hispanics is relevant for their even more neglected and vulnerable Native American ancestors along the American continent.

Abstract Objective To estimate the association between the aggregation and pair-wise combination of selected cardiovascular risk factors (CVRF) and 10-year all-cause mortality. Methods Secondary data analysis of the PERU MIGRANT study, a prospective population-based cohort. Ten-year all-cause mortality was determined for participants originally enrolled in the PERU MIGRANT Study (baseline in 2007) through the National Registry of Identification and Civil Status. The CVRF included hypertension, type 2 diabetes mellitus, hypercholesterolemia, and overweight/obesity. Exposures were composed of both the aggregation of the selected CVRF (one, two, and three or more CVRF) and pair-wise combinations of CVRF. Cox regression models were used to calculate hazard ratios (HR) and 95% confidence intervals (95% CI). Findings Of the 989 participants evaluated at baseline, 976 (98.8%) had information about vital status at 10 years of follow-up (9992.63 person-years), and 63 deaths were recorded. In the multivariable model, adjusting for sociodemographic and lifestyle variables, participants with two CVRF (HR: 2.48, 95% CI: 1.03–5.99), and those with three or more CVRF (HR: 3.93, 95% CI: 1.21–12.74) had higher all-cause mortality risk, compared to those without any CVRF. The pair-wise combinations associated with the highest risk of all-cause mortality, compared to those without such comorbidities, were hypertension with type 2 diabetes (HR: 11.67, 95% CI: 3.67–37.10), and hypertension with overweight/obesity (HR: 2.76, 95% CI: 1.18–6.71). Conclusions The aggregation of two or more CVRF and the combination of hypertension with type 2 diabetes or overweight/obesity were associated with an increased risk of 10-year all-cause mortality. These risk profiles will inform primary and secondary prevention strategies to delay mortality from cardiovascular risk factors.

Signals of antimicrobial resistance in pathogen genomes may be detectable before the organism evolves an antimicrobial resistance phenotype. Here, the authors investigate this hypothesis using Mycobacterium tuberculosis data from Peru and identify candidate “pre-resistance” markers.

Abstract Background The Tuberculosis (TB) burden in Peru is significant with respect to both disease morbidity and mortality. Furthermore the recent diversification of farming enterprise to include a wide range of animal species has necessitated the consideration of members of the Mycobacterium Tuberculosis Complex (MTBC) with the potential for zoonotic transmission. M. bovis and M. caprae, a lesser known member of the MTBC exhibit an exceptionally wide host spectrum in animals and are capable of causing disease in humans. M. bovis has a predictable resistance profile which includes resistance to pyrazinamide. Thus, failure to identify M. bovis as the causative agent in reported TB cases leads to higher levels of treatment failure and contributes to the transmission of drug-resistant TB. Case presentation Reported here are the clinical presentations, investigations and treatment histories of two patients identified from a population level genotyping study in Lima, Peru that were at the time of treatment thought to be M. tuberculosis patients but in retrospect were spectated using whole genome sequencing as M. caprae and M. Bovis. Conclusions The cases reported here constitute convincing evidence that M. caprae and M. bovis are causative agents of TB infection in humans in Peru and underscore the importance of species-level MTBC member identification to effectively control and treat zoonotic TB. Furthermore these cases highlight the challenges of using clinical risk factors to identify cases of zoonotic TB in humans as their clinical presentation and transmission history is often difficult to distinguish from anthroponotic TB.

Immunological mechanisms of susceptibility to nontuberculous mycobacterial (NTM) disease are poorly understood. To understand NTM pathogenesis, we evaluated innate and antigen-specific adaptive immune responses to Mycobacterium avium complex (MAC) in asymptomatic individuals with a previous history of MAC lung disease (MACDZ). We hypothesized that Mav-specific immune responses are associated with susceptibility to MAC lung disease. We measured MAC-, NTM-, or MAC/Mtb-specific T-cell responses by cytokine production, expression of surface markers, and analysis of global gene expression in 27 MACDZ individuals and 32 healthy controls. We also analyzed global gene expression in Mycobacterium avium-infected and uninfected peripheral blood monocytes from 17 MACDZ and 17 healthy controls. We were unable to detect increased T-cell responses against MAC-specific reagents in MACDZ compared to controls, while the responses to non-mycobacteria derived antigens were preserved. MACDZ individuals had a lower frequency of Th1 and Th1* T-cell populations. In addition, MACDZ subjects had lower transcriptional responses in PBMCs stimulated with a mycobacterial peptide pool (MTB300). By contrast, global gene expression analysis demonstrated upregulation of proinflammatory pathways in uninfected and M. avium-infected monocytes, i.e. a hyperinflammatory in vitro response, derived from MACDZ subjects compared to controls. Together, these data suggest a novel immunologic defect which underlies MAC pathogenesis and includes concurrent innate and adaptive dysregulation which persists years after completion of treatment.

Optimal control strategies for Taenia solium taeniasis and cysticercosis have not been determined. We conducted a 2-year cluster randomized trial in Peru by assigning 23 villages to 1 of 3 geographically targeted intervention approaches. For ring screening (RS), participants living near pigs with cysticercosis were screened for taeniasis; identified cases were treated with niclosamide. In ring treatment (RT), participants living near pigs with cysticercosis received presumptive treatment with niclosamide. In mass treatment (MT), participants received niclosamide treatment every 6 months regardless of location. In each approach, half the villages received targeted or mass oxfendazole for pigs (6 total study arms). We noted significant reductions in seroincidence among pigs in all approaches (67.1% decrease in RS, 69.3% in RT, 64.7% in MT; p

The efficacy of two locally produced oxfendazole (OFZ) formulations against cysticercosis at 22,5% and 10%, versus a commercial formulation (Synanthic 9,06%) was evaluated in twenty-two naturally infected pigs that received a single oral dose of 30 mg/kg. Pigs were sacrificed at eight weeks post-treatment to evaluate the cysts found in their carcasses, and to determine the cysticidal efficacy, which was defined as the proportion of degenerated cysts over total cysts. Only degenerated cysts were found in muscle, heart, and tongue of pigs treated with OFZ in all groups, which shows an efficacy of 100%. Viable and degenerated cysts were found in brains, being the efficacy lower in all groups (65% [commercial OFZ], 47% [local OFZ 22.5%] and 31% [local OFZ 10%], p = 0.355). Locally produced OFZ formulations were similarly effective to the commercial formulation and may provide a practical alternative for the treatment of porcine cysticercosis.

Background: Chagas disease is an endemic protozoan disease with high prevalence in Latin America. Of those infected, 20–30% will develop chronic Chagas cardiomyopathy (CCC) however, prediction using existing clinical criteria remains poor. In this study, we investigated the utility of left ventricular (LV) echocardiographic speckle-tracking global longitudinal strain (GLS) for early detection of CCC. Methods and results: 139 asymptomatic T. cruzi seropositive subjects with normal heart size and normal LV ejection fraction (EF) (stage A or B) were enrolled in this prospective observational study and underwent paired echocardiograms at baseline and 1-year follow-up. Progressors were participants classified as stage C or D at follow-up due to development of symptoms of heart failure, cardiomegaly, or decrease in LVEF. LV GLS was calculated as the average peak systolic strain of 16 LV segments. Measurements were compared between participants who progressed and did not progress by two-sample t-test, and the odds of progression assessed by multivariable logistic regression. Of the 139 participants, 69.8% were female, mean age 55.8 ± 12.5 years, with 12 (8.6%) progressing to Stage C or D at follow-up. Progressors tended to be older, male, with wider QRS duration. LV GLS was −19.0% in progressors vs. –22.4% in non-progressors at baseline, with 71% higher odds of progression per +1% of GLS (adjusted OR 1.71, 95% CI 1.20–2.44, p = 0.003). Conclusion: Baseline LV GLS in participants with CCC stage A or B was predictive of progression within 1-year and may guide timing of clinical follow-up and promote early detection or treatment.

Background: Vertical transmission of Trypanosoma cruzi infection from mother to infant accounts for a growing proportion of new Chagas disease cases. However, no systematic reviews of risk factors for T. cruzi vertical transmission have been performed. Methods: We performed a systematic review of the literature in PubMed, LILACS, and Embase databases, following PRISMA guidelines. Studies were not excluded based on language, country of origin, or publication date. Results: Our literature review yielded 27 relevant studies examining a wide variety of risk factors, including maternal age, parasitic load, immunologic factors and vector exposure. Several studies suggested that mothers with higher parasitic loads may have a greater risk of vertical transmission. A meta-analysis of 2 studies found a significantly higher parasitic load among transmitting than non-transmitting mothers with T. cruzi infection. A second meta-analysis of 10 studies demonstrated that maternal age was not significantly associated with vertical transmission risk. Conclusions: The literature suggests that high maternal parasitic load may be a risk factor for congenital Chagas disease among infants of T. cruzi seropositive mothers. Given the considerable heterogeneity and risk of bias among current literature, additional studies are warranted to assess potential risk factors for vertical transmission of T. cruzi infection.

Background Neurocysticercosis (NCC) is the infection of the human central nervous system (CNS) by Taenia solium larvae that cause significant neurological morbidity. Studies on NCC pathophysiology, host-parasite interactions or therapeutic agents are limited by the lack of suitable animal models. We have previously reported that carotid injection of activated T. solium oncospheres directs parasites into the CNS and consistently reproduces NCC. This study assessed the minimal dose required to consistently obtain NCC by intracarotid oncosphere injection and compared antigen and antibody response profiles by dose-group. Methods/Principal findings Three groups of pigs were infected with either 2500 (n = 10), 5000 (n = 11), or 10000 (n = 10) oncospheres. Two pigs died during the study. Necropsy exam at day 150 post-infection (PI) demonstrated viable NCC in 21/29 pigs (72.4%), with higher NCC rates with increasing oncosphere doses (4/9 [44.4%], 9/11 [81.8%] and 8/9 [88.9%] for 2500, 5000, and 10000 oncospheres respectively, P for trend = 0.035). CNS cyst burden was also higher in pigs with increasing doses (P for trend = 0.008). Viable and degenerated muscle cysticerci were also found in all pigs, with degenerated cysticerci more frequent in the 2500 oncosphere dose-group. All pigs were positive for circulating parasite antigens on ELISA (Ag-ELISA) from day 14 PI; circulating antigens markedly increased at day 30 PI and remained high with plateau levels in pigs infected with either 5000 or 10000 oncospheres, but not in pigs infected with 2500 oncospheres. Specific antibodies appeared at day 30 PI and were not different between dose-groups. Conclusion/Significance Intracarotid injection of 5000 or more oncospheres produces high NCC rates in pigs with CNS cyst burdens like those usually found in human NCC, making this model appropriate for studies on the pathogenesis of NCC and the effects of antiparasitic treatment. Author summary Neurocysticercosis (NCC) is the infection of the central nervous system (CNS) with Taenia solium larvae and is considered a neglected disease that causes significant neurological morbidity in humans. Animal models are essential to better understand the pathophysiological processes that occur during NCC infection, disease progression and to evaluate the effects of antiparasitic treatment. Here, we demonstrated that by injecting 5000 or more activated T. solium oncospheres into the carotid artery of pigs we consistently reproduced NCC in a number that closely resemble human infection. All cysticerci found in the CNS were apparently viable, whereas in the musculature viable and degenerated cysticerci were found. Serum antigens in experimentally infected pigs were detected as early as 14 days post–infection and remained high in NCC pigs until necropsy. Histological analysis of brain cysticerci showed different degrees of inflammatory cell infiltration adjacent to the cyst wall, mostly composed of eosinophils, lymphocytes, and macrophages, whereas most of the cysticerci were apparently intact with cyst wall and neck without damage. Our findings demonstrated that the intracarotid pig model is suitable for studies on the pathogenesis and antiparasitic treatment in NCC.

Abstract 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.

Norovirus is a major cause of acute gastroenteritis. Human noroviruses present >30 different genotypes, with a single genotype (GII.4) predominating worldwide. Concurrent outbreaks of norovirus are often associated with the emergence of new viruses. While different hypotheses have been presented, the source of new mutations in noroviruses is still unknown. In this study, we applied high-resolution sequencing to determine the intra-host viral diversity presented by noroviruses during the acute and shedding phase of infection in children. Profiling viral intra-host diversification at nearly full genome level indicated that GII.4 viruses presented dynamic intra-host variation, while non-GII.4 viruses presented minimal variation throughout the infection. Notably, the intra-host genetic variation during the shedding phase recapitulates the genetic diversity observed at the global level, particularly those mapping at the VP1 antigenic sites. Thus the intra-host evolution in healthy children explains the source of norovirus mutations that results in diversification at the global scale.

Abstract Chagas disease is considered the most important parasitic disease in Latin America. The protozoan agent, Trypanosoma cruzi, comprises six genetic lineages, TcI-TcVI. Genotyping to link lineage(s) to severity of cardiomyopathy and gastrointestinal pathology is impeded by the sequestration and replication of T. cruzi in host tissues. We describe serology specific for TcI, the predominant lineage north of the Amazon, based on expression of recombinant trypomastigote small surface antigen (gTSSA-I) in the eukaryote Leishmania tarentolae, to allow realistic glycosylation and structure of the antigen. Sera from TcI-endemic regions recognised gTSSA-I (74/146; 50.7%), with no cross reaction with common components of gTSSA-II/V/VI recombinant antigen. Antigenicity was abolished by chemical (periodate) oxidation of gTSSA-I glycosylation but retained after heat-denaturation of conformation. Conversely, non-specific recognition of gTSSA-I by non-endemic malaria sera was abolished by heat-denaturation. TcI-specific serology facilitates investigation between lineage and diverse clinical presentations. Glycosylation cannot be ignored in the search for immunogenic antigens.

Summary: Background: Limited information exists about the incidence of first-ever stroke at the population level, particularly in low- and middle-income countries (LMIC). Longitudinal data from the CRONICAS Cohort Study includes both altitude and urbanization and allows a detailed assessment of stroke incidence in resource constrained settings. The aim of this study was to estimate the incidence and explore risk factors of first-ever stroke at the population level in Peru. Methods: Stroke was defined using a standardised approach based on information from cohort participants or family members. This information was adjudicated centrally by trained physicians using common definitions. Time of follow-up was calculated as the difference between date of enrolment and the reported date of the stroke event. Unstandardised and age-standardised, first-ever stroke incidence rate and 95% confidence intervals (95% CI) were calculated. Generalized linear models, assuming Poisson distribution and link log, were utilized to determine potential factors to develop stroke. Findings: 3,601 individuals were originally enrolled in the cohort and 2,471 provided data for the longitudinal analysis. The median time of follow-up was 7.0 (range: 1 - 9) years, accruing a total of 17,308 person-years. During follow-up, there were 25 incident cases of stroke, resulting in an age-standardised incidence of stroke of 98.8 (95% CI: 63.8–154.0) per 100,000 person-years. After adjustment by age and sex, stroke incidence was higher among people with hypertension (incidence risk ratio (IRR) = 5.18; 95% CI: 1.89 – 14.16), but lower among people living at high altitude (IRR = 0.09; 95% CI: 0.01 – 0.63). Interpretation: Our results indicate a high incidence of first-ever strokes in Peruvian general population. These results are consistent with the estimates found in previous LMIC reports. Our study also found a contributing role of hypertension, increasing the risk of having a first-ever stroke. This work further advances the field of stroke epidemiology by identifying high altitude as a factor related to lower incidence of stroke in a longitudinal study. However, this information needs to be considered with cautions because of the study limitations.

Abstract Background Indoor air pollution is an important risk factor for health in low- and middle-income countries. Methods We measured indoor fine particulate matter (PM2.5) and carbon monoxide (CO) concentrations in 617 houses across four settings with varying urbanisation, altitude, and biomass cookstove use in Peru, between 2010 and 2016. We assessed the associations between indoor pollutant concentrations and blood pressure (BP), exhaled carbon monoxide (eCO), C-reactive protein (CRP), and haemoglobin A1c (HbA1c) using multivariable linear regression among all participants and stratifying by use of biomass cookstoves. Results We found high concentrations of indoor PM2.5 across all four settings (geometric mean ± geometric standard deviation of PM2.5 daily average in μg/m3): Lima 41.1 ± 1.3, Tumbes 35.8 ± 1.4, urban Puno 14.1 ± 1.7, and rural Puno 58.8 ± 3.1. High indoor CO concentrations were common in rural households (geometric mean ± geometric standard deviation of CO daily average in ppm): rural Puno 4.9 ± 4.3. Higher indoor PM2.5 was associated with having a higher systolic BP (1.51 mmHg per interquartile range (IQR) increase, 95% CI 0.16 to 2.86), a higher diastolic BP (1.39 mmHg higher DBP per IQR increase, 95% CI 0.52 to 2.25), and a higher eCO (2.05 ppm higher per IQR increase, 95% CI 0.52 to 3.57). When stratifying by biomass cookstove use, our results were consistent with effect measure modification in the association between PM2.5 and eCO: among biomass users eCO was 0.20 ppm higher per IQR increase in PM2.5 (95% CI − 2.05 to 2.46), and among non-biomass users eCO was 5.00 ppm higher per IQR increase in PM2.5 (95% CI 1.58 to 8.41). We did not find associations between indoor air concentrations and CRP or HbA1c outcomes. Conclusions Excessive indoor concentrations of PM2.5 are widespread in homes across varying levels of urbanisation, altitude, and biomass cookstove use in Peru and are associated with worse BP and higher eCO.

Chagas disease (CD), caused by the protozoan Trypanosoma cruzi , is a public health concern, mainly among countries in South and Central America. However, despite the large number of immigrants from endemic countries living in the USA, awareness of CD is poor in the medical community, and therefore it is significantly underdiagnosed. To avoid the catastrophic cardiac complications of CD and to prevent maternal–fetal transmission, widespread educational programs highlighting the need for diagnosis are urgently needed.

We report multiple nontypeable genotype II noroviruses circulating in South America; nucleotides differed by >25% from those of other genotypes. These viruses have been circulating in the Americas for ≈20 years and show recombination with other genotypes. Clues to norovirus natural history can guide development of treatment and prevention plans.

The widespread and poorly regulated use of antibiotics in animal production in low- and middle-income countries (LMICs) is increasingly associated with the emergence and dissemination of antibiotic resistance genes (ARGs) in retail animal products. Here, we compared Escherichia coli from chickens and humans with varying levels of exposure to chicken meat in a low-income community in the southern outskirts of Lima, Peru. We hypothesize that current practices in local poultry production result in highly resistant commensal bacteria in chickens that can potentially colonize the human gut. E. coli was isolated from cloacal swabs of non-organic (n = 41) and organic chickens (n = 20), as well as from stools of market chicken vendors (n = 23), non-vendors (n = 48), and babies (n = 60). 315 E. coli isolates from humans (n = 150) and chickens (n = 165) were identified, with chickens showing higher rates of multidrug-resistant and extended-spectrum beta-lactamase phenotypes. Non-organic chicken isolates were more resistant to most antibiotics tested than human isolates, while organic chicken isolates were susceptible to most antibiotics. Whole-genome sequencing of 118 isolates identified shared phylogroups between human and animal populations and 604 ARG hits across genomes. Resistance to florfenicol (an antibiotic commonly used as a growth promoter in poultry but not approved for human use) was higher in chicken vendors compared to other human groups. Isolates from non-organic chickens contained genes conferring resistance to clinically relevant antibiotics, including mcr-1 for colistin resistance, blaCTX-M ESBLs, and blaKPC-3 carbapenemase. Our findings suggest that E. coli strains from market chickens are a potential source of ARGs that can be transmitted to human commensals.

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 (NV-IgA) in breast milk. Methods: Ninety-five breast milk samples collected from mothers enrolled in a 2016–2017 Peruvian birth cohort study were tested for total IgA and NV-IgA by ELISA using GII·4 variants and non-GII·4 genotype virus-like particles (VLPs). Breast milk samples were grouped according to the 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-IgA were compared among groups. The cross-reactivity was estimated based on the correlation of ratio between NV-IgA against GII·4 variants and non-GII·4 genotype VLPs. Findings: NV-IgA had high positivity rates against different VLPs, especially against GII (89–100%). The NV+D- group had higher percent positivity (89% vs. 61%, p=0·03) and median titer (1:100 vs 1:50, p=0·03) of NV-IgA than the NV+D+ group against GI·1 VLPs. A relatively high correlation between different GII·4 variants (0·87) and low correlation between genogroups (0·23–0·37) were observed. Interpretation: Mothers with high positivity rates and titers of NV-IgA in breast milk had NV infected infants with reduced diarrheal symptoms. Antigenic relatedness to the genetic diversity of human norovirus was suggested.Funding 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

Poultry farming represents Peru’s primary food animal production industry, where antimicrobial growth promoters are still commonly used, exerting selective pressure on intestinal microbial populations. Consumption and direct animal-to-human transmission have been reported, and farmworkers are at high risk of colonization with resistant bacteria. We conducted a cross-sectional survey among 54 farmworkers to understand their current antimicrobial resistance (AMR) awareness in Ica, Peru. To gain insight into the potential work-related risk of exposure to bacteria, we also measured the AMR rates in Escherichia coli isolated among 50 broiler chickens. Farmworkers were unaware of antimicrobial resistance (31.5%) or antibiotic resistance (16.7%) terms. Almost two-thirds (61%) consumed antibiotics during the previous month, and only 42.6% received a prescription from a healthcare professional. A total of 107 E. coli chicken isolates were obtained, showing a high frequency of multidrug-resistant (89.7%) and extended-spectrum beta-lactamase (ESBL) production (71.9%). Among ESBL-producer isolates, 84.4% carried the blaCTX-M gene. Results identified gaps in knowledge that reflect the need for interventions to increase antimicrobial awareness among poultry farmworkers. The high AMR rates among E. coli isolates highlight the need to reduce antimicrobial use in poultry farms. Our findings reveal a critical need for effective policy development and antimicrobial stewardship interventions in poultry production in Ica, Peru.

Trypanosoma cruzi infection leads to Chagas disease (CD), a neglected tropical infection of significant public health importance in South and Central America and other, non-endemic, countries. Pregnant women and their children are of particular importance to screen as T. cruzi can be transmitted vertically. The objective of this study was to screen for T. cruzi infection among pregnant women from endemic areas seen at the Hospital General de Mexico for prenatal care, so that they and their children may be quickly connected to CD treatment. Pregnant women were recruited through the hospital prenatal clinic and screened for T. cruzi infection using a series of serological and molecular tests. Of 150 screened patients, mean age 26.8 (SD 6.4), 30 (20.0%) were positive by at least one diagnostic test. Of these, only nine (6%) were positive as determined by PCR. Diagnosis of chronic CD is difficult in endemic places like Mexico due to the limitations of current commercially available diagnostic tests. Further evaluation of diagnostic performance of various assays could improve current CD diagnostic algorithms and proper care management in these regions. Genetic variability in the parasite may also play a role in the differing assay performances seen in this study, and this may be a valuable avenue of further research.

Background: Novel approaches to reduce diabetic foot ulcers (DFU) in low- and middle-income countries are needed. Our objective was to compare incidence of DFUs in the thermometry plus mobile health (mHealth) reminders (intervention) vs. thermometry-only (control). Methods: We conducted a randomized trial enrolling adults with type 2 diabetes mellitus at risk of foot ulcers (risk groups 2 or 3) but without foot ulcers at the time of recruitment, and allocating them to control (instruction to use a liquid crystal-based foot thermometer daily) or intervention (same instruction supplemented with text and voice messages with reminders to use the device and messages to promote foot care) groups, and followed for 18 months. The primary outcome was time to occurrence of DFU. A process evaluation was also conducted. Results: A total of 172 patients (63% women, mean age 61 years) were enrolled; 86 to each study group. More patients enrolled in the intervention arm had a history of previous DFU (66% vs. 48%). Follow-up for the primary endpoint was complete for 158 of 172 participants (92%). Adherence to ≥80% of daily temperature measurements was 87% (103 of 118) among the study participants who returned the logbook. DFU cumulative incidence was 24% (19 of 79) in the intervention arm and 11% (9 of 79) in the control arm. After adjusting for history of foot ulceration and study site, the hazard ratio (HR) for DFU was 1.44 (95% CI 0.65, 3.22). Conclusions: In our study, conducted in a low-income setting, the addition of mHealth to foot thermometry was not effective in reducing foot ulceration. Importantly, there was a higher rate of previous DFU in the intervention group, the adherence to thermometry was high, and the expected rates of DFU used in our sample size calculations were not met. Trial registration: ClinicalTrials.gov NCT02373592 (27/02/2015)

Background: Food insecurity is a major global public health issue. Social capital has been identified as central to maintaining food security across a wide range of low- and middle-income country contexts, but few studies have examined this relationship through sociocentric network analysis. Objective: We investigated relationships between household- and community-level social connectedness, household food security, and household income; and tested the hypothesis that social connectedness modified the relationship between income and food security. Methods: A cross-sectional census with an embedded questionnaire to capture social relationships was conducted among eleven peri-urban communities. Community connectedness was related to study outcomes of food security and per-capita income through regression models. Results: Of 1520 households identified, 1383 were interviewed (91.0%) and 1272 (83.9%) provided complete data. Households in the youngest communities had the most total contacts, and the highest proportion of contacts outside of the community. Household income was also associated with more outside-community contacts (0.05 more contacts per standard deviation increase in income, p

Neurocysticercosis is a nervous system infection caused by the larvae (cysticercus) of the pork tapeworm (Taenia solium). Neurocysticercosis is the primary cause of acquired epilepsy worldwide and, therefore, a global public health problem. On the other hand, T. solium taeniasis/cysticercosis is one of very few infectious diseases considered to be potentially eradicable. Recently, a large-scale elimination program in Tumbes, Peru, demonstrated the feasibility of interrupting transmission. Based on these advances, a series of initial guidelines are proposed aimed at setting out the foundations for regional and national taeniasis/cysticercosis control programs, with simple and feasible local interventions as a starting point.

Abstract Background Delays in receiving adequate care for children suffering from pneumonia can be life threatening and have been described associated with parents’ limited education and their difficulties in recognizing the severity of the illness. The “three delays” was a model originally proposed to describe the most common determinants of maternal mortality, but has been adapted to describe delays in the health seeking process for caregivers of children under five. This study aims to explore the caregivers’ perceived barriers for seeking and receiving health care services in children under five years old admitted to a referral hospital for community-acquired pneumonia in the Peruvian Amazon Region using the three-delays model framework. Methods There were two parts to this mixed-method, cross-sectional, hospital-based study. First, medical charts of 61 children (1 to 60 months old) admitted for pneumonia were reviewed, and clinical characteristics were noted. Second, to examine health care-seeking decisions and actions, as well as associated delays in the process of obtaining health care services, we interviewed 10 of the children’s caregivers. Results Half of the children in our study were 9 months old or less. Main reasons for seeking care at the hospital were cough (93%) and fever (92%). Difficulty breathing and fast breathing were also reported in more than 60% of cases. In the interviews, caregivers reported delays of 1 to 14 days to go to the closest health facility. Factors perceived as causes for delays in deciding to seek care were apparent lack of skills to recognize signs and symptoms and of confidence in the health system, and practicing self-medication. No delays in reaching a health facility were reported. Once the caregivers reached a health facility, they perceived lack of competence of medical staff and inadequate treatment provided by the primary care physicians. Conclusion According to caregivers, the main delays to get health care services for pneumonia among young children were identified in the initial decision of caregivers to seek healthcare and in the health system to provide it. Specific interventions targeted to main barriers may be useful for reducing delays in providing appropriate health care for children with pneumonia.

Abstract Background The Lives Saved Tool (LiST) is a widely used resource for evidence-based decision-making regarding health program scale-up in low- and middle-income countries. LiST estimates the impact of specified changes in intervention coverage on mortality and stunting among children under 5 years of age. We aimed to improve the estimates of the parameters in LiST that determine the rate at which the effects of interventions to prevent stunting attenuate as children get older. Methods We identified datasets with serial measurements of children’s lengths or heights and used random effects models and restricted cubic splines to model the growth trajectories of children with at least six serial length/height measurements. We applied WHO growth standards to both measured and modelled (smoothed) lengths/heights to determine children’s stunting status at multiple ages (1, 6, 12, 24 months). We then calculated the odds ratios for the association of stunting at one age point with stunting at the next (“stunting-to-stunting ORs”) using both measured and smoothed data points. We ran analyses in LiST to compare the impact on intervention effect attenuation of using smoothed rather than measured stunting-to-stunting ORs. Results A total of 21,786 children with 178,786 length/height measurements between them contributed to our analysis. The odds of stunting at a given age were strongly related to whether a child is stunted at an earlier age, using both measured and smoothed lengths/heights, although the relationship was stronger for smoothed than measured lengths/heights. Using smoothed lengths/heights, we estimated that children stunted at 1 month have 45 times the odds of being stunted at 6 months, with corresponding odds ratios of 362 for the period 6 to 12 months and 175 for the period 12 to 24 months. Using the odds ratios derived from the smoothed data in LiST resulted in a somewhat slower attenuation of intervention effects over time, but substantial attenuation was still observed in the LiST outputs. For example, in Mali the effect of effectively eliminating SGA births reduced prevalence of stunting at age 59 months from 44.4% to 43.7% when using odds ratios derived from measured lengths/heights and from 44.4% to 41.9% when using odds ratios derived from smoothed lengths/heights. Conclusions Smoothing of children’s measured lengths/heights increased the strength of the association between stunting at a given age and stunting at an earlier age. Using odds ratios based on smoothed lengths/heights in LiST resulted in a small reduction in the attenuation of intervention effects with age and thus some increase in the estimated benefits, and may better reflect the true benefits of early nutritional interventions.

Abstract Background Chronic Kidney Disease (CKD) represents a great burden for the patient and the health system, particularly if diagnosed at late stages. Consequently, tools to identify patients at high risk of having CKD are needed, particularly in limited-resources settings where laboratory facilities are scarce. This study aimed to develop a risk score for prevalent undiagnosed CKD using data from four settings in Peru: a complete risk score including all associated risk factors and another excluding laboratory-based variables. Methods Cross-sectional study. We used two population-based studies: one for developing and internal validation (CRONICAS), and another (PREVENCION) for external validation. Risk factors included clinical- and laboratory-based variables, among others: sex, age, hypertension and obesity; and lipid profile, anemia and glucose metabolism. The outcome was undiagnosed CKD: eGFR

Abstract Background Tuberculosis (TB) is a major global health problem and drug resistance compromises the efforts to control this disease. Pyrazinamide (PZA) is an important drug used in both first and second line treatment regimes. However, its complete mechanism of action and resistance remains unclear. Results We genotyped and sequenced the complete genomes of 68 M. tuberculosis strains isolated from unrelated TB patients in Peru. No clustering pattern of the strains was verified based on spoligotyping. We analyzed the association between PZA resistance with non-synonymous mutations and specific genes. We found mutations in pncA and novel genes significantly associated with PZA resistance in strains without pncA mutations. These included genes related to transportation of metal ions, pH regulation and immune system evasion. Conclusions These results suggest potential alternate mechanisms of PZA resistance that have not been found in other populations, supporting that the antibacterial activity of PZA may hit multiple targets.

Abstract Background Diet and activity are thought to worsen with urbanization, thereby increasing risk of obesity and chronic diseases. A better understanding of dietary and activity patterns across the urbanization divide may help identify pathways, and therefore intervention targets, leading to the epidemic of overweight seen in low- and middle-income populations. Therefore, we sought to characterize diet and activity in a population-based study of urban and rural residents in Puno, Peru. Methods We compared diet and activity in 1005 (503 urban, 502 rural) participants via a lifestyle questionnaire. We then recruited an age- and sex-stratified random sample of 50 (25 urban, 25 rural) participants to further characterize diet and activity. Among these participants, diet composition and macronutrient intake was assessed by three non-consecutive 24-h dietary recalls and physical activity was assessed using Omron JH-720itc pedometers. Results Among 1005 participants, we found that urban residents consumed protein-rich foods, refined grains, sugary items, and fresh produce more frequently than rural residents. Among the 50 subsample participants, urban dwellers consumed more protein (47 vs. 39 g; p = 0.05), more carbohydrates (280 vs. 220 g; p = 0.03), more sugary foods (98 vs. 48 g, p = 0.02) and had greater dietary diversity (6.4 vs 5.8; p = 0.04). Rural subsample participants consumed more added salt (3.1 vs 1.7 g, p = 0.006) and tended to consume more vegetable oil. As estimated by pedometers, urban subsample participants burned fewer calories per day (191 vs 270 kcal, p = 0.03). Conclusions Although urbanization is typically thought to increase consumption of fat, sugar and salt, our 24-h recall results were mixed and showed lower levels of obesity in rural Puno were not necessarily indicative of nutritionally-balanced diets. All subsample participants had relatively traditional lifestyles (low fat intake, limited consumption of processed foods and frequent walking) that may play a role in chronic disease outcomes in this region.

Abstract Background Previous studies have found mixed results about cigarette and alcohol consumption patterns among rural-to-urban migrants. Moreover, there are limited longitudinal data about consumption patterns in this population. As such, this study aimed to compare the smoking and heavy drinking prevalence among rural, urban, and rural-to-urban migrants in Peru, as well as the smoking and heavy drinking incidence in a 5-year follow-up. Methods We analyzed the PERU MIGRANT Study data from rural, urban, and rural-to-urban migrant populations in Peru. The baseline study was carried out in 2006–2007 and follow-up was performed five years later. For the baseline data analysis, the prevalence of lifetime smoking, current smokers, and heavy drinking was compared by population group using prevalence ratios (PR) and 95% confidence intervals (95% CI). For the longitudinal analysis, the incidence of smoking and heavy drinking was compared by population group with risk ratios (RR) and 95% CI. Poisson regression with robust variance was used to calculate both PRs and RRs. Results We analyzed data from 988 participants: 200 rural dwellers, 589 migrants, and 199 urban dwellers. Compared with migrants, lifetime smoking prevalence was higher in the urban group (PR = 2.29, 95% CI = 1.64–3.20), but lower in the rural group (PR = 0.55, 95% CI = 0.31–0.99). Compared with migrants, the urban group had a higher current smoking prevalence (PR = 2.29, 95% CI = 1.26–4.16), and a higher smoking incidence (RR = 2.75, 95% CI = 1.03–7.34). Current smoking prevalence and smoking incidence showed no significant difference between rural and migrant groups. The prevalence and incidence of heavy drinking was similar across the three population groups. Conclusions Our results show a trend in lifetime smoking prevalence (urban > migrant > rural), while smoking incidence was similar between migrant and rural groups, but higher in the urban group. In addition, our results suggest that different definitions of smoking status could lead to different smoking rates and potentially different measures of association. The prevalence and incidence of heavy drinking were similar between the three population groups.

Abstract 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