Body Composition Trajectories During the First 23 Months of Life Differ by HIV Exposure Among Infants in Western Kenya: A Prospective Study.

BACKGROUND: Infants who are HIV-exposed and uninfected have suboptimal growth patterns compared to those who are HIV-unexposed and uninfected. However, little is known about how these patterns persist beyond 1 year of life. OBJECTIVES: This study aimed to examine whether infant body composition and growth trajectories differed by HIV exposure during the first 2 years of life among Kenyan infants using advanced growth modeling. METHODS: Repeated infant body composition and growth measurements (mean: 6; range: 2-7) were obtained from 6 weeks to 23 months in the Pith Moromo cohort in Western Kenya (n = 295, 50% HIV-exposed and uninfected, 50% male). Body composition trajectory groups were fitted using latent class mixed modeling (LCMM) and associations between HIV exposure and growth trajectories were examined using logistic regression analysis. RESULTS: All infants exhibited poor growth. However, HIV-exposed infants generally grew suboptimally than unexposed infants. Across all body composition models except for the sum of skinfolds, HIV-exposed infants had a higher likelihood of belonging to the suboptimal growth groups identified by LCMM than the HIV-unexposed infants. Notably, HIV-exposed infants were 3.3 times more likely (95% CI: 1.5-7.4) to belong to the length-for-age z-score growth class that remained at a z-score of < -2, indicating stunted growth. HIV-exposed infants were also 2.6 times more likely (95% CI: 1.2-5.4) to belong to the weight-for-length-for-age z-score growth class that remained between 0 and -1, and were 4.2 times more likely (95% CI: 1.9-9.3) to belong to the weight-for-age z-score growth class that indicated poor weight gain besides stunted linear growth. CONCLUSIONS: In a cohort of Kenyan infants, HIV-exposed infants grew suboptimally compared to HIV-unexposed infants beyond 1 year of age. These growth patterns and longer-term effects should be further investigated to support the ongoing efforts to reduce early-life HIV exposure-related health disparities.

Preclinical trial of a MAP4K4 inhibitor to reduce infarct size in the pig: does cardioprotection in human stem cell-derived myocytes predict success in large mammals?

Reducing infarct size (IS) by interfering with mechanisms for cardiomyocyte death remains an elusive goal. DMX-5804, a selective inhibitor of the stress-activated kinase MAP4K4, suppresses cell death in mouse myocardial infarction (MI), human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs), and 3D human engineered heart tissue, whose fidelity to human biology is hoped to strengthen the route to clinical success. Here, DMX-10001, a soluble, rapidly cleaved pro-drug of DMX-5804, was developed for i.v. testing in large-mammal MI. Following pharmacodynamic studies, a randomized, blinded efficacy study was performed in swine subjected to LAD balloon occlusion (60 min) and reperfusion (24 h). Thirty-six animals were enrolled; 12 were excluded by pre-defined criteria, death before infusion, or technical issues. DMX-10001 was begun 20 min before reperfusion (30 min, 60 mg/kg/h; 23.5 h, 17 mg/kg/h). At all times tested, beginning 30 min after the start of infusion, DMX-5804 concentrations exceeded > fivefold the levels that rescued hPSC-CMs and reduced IS in mice after oral dosing with DMX-5804 itself. No significant reduction occurred in IS or no-reflow corrected for the area at ischemic risk, even though DMX-10001 reduced IS, expressed in grams or % of LV mass, by 27%. In summary, a rapidly cleaved pro-drug of DMX-5804 failed to reduce IS in large-mammal MI, despite exceeding the concentrations for proven success in both mice and hPSC-CMs.

SeqSero2: Rapid and Improved Salmonella Serotype Determination Using Whole-Genome Sequencing Data.

SeqSero, launched in 2015, is a software tool for Salmonella serotype determination from whole-genome sequencing (WGS) data. Despite its routine use in public health and food safety laboratories in the United States and other countries, the original SeqSero pipeline is relatively slow (minutes per genome using sequencing reads), is not optimized for draft genome assemblies, and may assign multiple serotypes for a strain. Here, we present SeqSero2 (github.com/denglab/SeqSero2; denglab.info/SeqSero2), an algorithmic transformation and functional update of the original SeqSero. Major improvements include (i) additional sequence markers for identification of Salmonella species and subspecies and certain serotypes, (ii) a k-mer based algorithm for rapid serotype prediction from raw reads (seconds per genome) and improved serotype prediction from assemblies, and (iii) a targeted assembly approach for specific retrieval of serotype determinants from WGS for serotype prediction, new allele discovery, and prediction troubleshooting. Evaluated using 5,794 genomes representing 364 common U.S. serotypes, including 2,280 human isolates of 117 serotypes from the National Antimicrobial Resistance Monitoring System, SeqSero2 is up to 50 times faster than the original SeqSero while maintaining equivalent accuracy for raw reads and substantially improving accuracy for assemblies. SeqSero2 further suggested that 3% of the tested genomes contained reads from multiple serotypes, indicating a use for contamination detection. In addition to short reads, SeqSero2 demonstrated potential for accurate and rapid serotype prediction directly from long nanopore reads despite base call errors. Testing of 40 nanopore-sequenced genomes of 17 serotypes yielded a single H antigen misidentification.IMPORTANCE Serotyping is the basis of public health surveillance of Salmonella It remains a first-line subtyping method even as surveillance continues to be transformed by whole-genome sequencing. SeqSero allows the integration of Salmonella serotyping into a whole-genome-sequencing-based laboratory workflow while maintaining continuity with the classic serotyping scheme. SeqSero2, informed by extensive testing and application of SeqSero in the United States and other countries, incorporates important improvements and updates that further strengthen its application in routine and large-scale surveillance of Salmonella by whole-genome sequencing.

Decreased consumption of common weaning foods is associated with poor linear growth among HIV-exposed infants participating in the Kigali antiretroviral and breastfeeding assessment for the elimination of HIV (Kabeho) study.

OBJECTIVE: The World Health Organization recommends that complementary foods that are adequate, safe, and appropriate be introduced to infants at age 6 months. Using an innovative modeling technique, we examine patterns of nutrient intake in HIV-exposed and uninfected (HEU) infants and establish their relationship with growth. METHODS: Single-day dietary recalls and anthropometrics were collected every two to 3 months from 543 infants living in Kigali, Rwanda, and attending clinics for the prevention of mother-to-child HIV transmission. A common weaning food index (CWFI) was calculated in grams and nutrient density for infants to reflect the extent to which the infants consumed the weaning foods typical of this population at ages 6 to 10, 11 to 15, and 16 to 20 months. Regressions among the CWFI, length-for-age z-scores (LAZ), and weight-for-length z-scores (WLZ) were conducted to estimate the relationship between the dietary patterns and growth. RESULTS: Mean absolute intake of zinc and calcium from complementary foods was insufficient. Increasing CWFI was related to increasing cow milk consumption. The density CWFI showed a decrease in the density of iron and folate as infants consume more of the weaning foods typical of this population. Density CWFI, breastfeeding, and caloric intake act on early LAZ and WLZ and interact with one another. Among breastfed infants, those who consume little of the common weaning foods and have a high caloric intake develop deficits in LAZ and have an elevated WLZ. CONCLUSIONS: A diet that is more dominated by the typical weaning foods of this population may support a healthy growth pattern.

Determinants of growth in HIV-exposed and HIV-uninfected infants in the Kabeho Study.

HIV-exposed and HIV-uninfected (HEU) infants may be at increased risk of poor health and growth outcomes. We characterized infant growth trajectories in a cohort of HEU infants to identify factors associated with healthy growth. HIV-positive women participating in prevention of mother-to-child HIV transmission programmes in Kigali, Rwanda, were followed until their infants were 2 years old. Infant anthropometrics were regularly collected. Latent class analysis was used to categorize infant growth trajectories. Multiple logistic regression was used to estimate the odds of infants belonging to each growth trajectory class. On average, this population of HEU infants had moderate linear growth faltering, but only modest faltering in weight, resulting in mean weight-for-length z-score (WLZ) above the World Health Organization (WHO) median. Mean WLZ was 0.53, and mean length-for-age z-score (LAZ) was -1.14 over the first 2 years of life. We identified four unique WLZ trajectories and seven trajectories in LAZ. Low neonatal weight-for-age and a high rate of illness increased the likelihood that infants were in the lightest WLZ class. Shorter mothers were more likely to have infants with linear growth faltering. Female infants who were older at the end of exclusive breastfeeding were more likely to be in the second tallest LAZ class. In conclusion, the current WHO recommendations of Option B+ and extended breastfeeding may induce higher WLZ and lower LAZ early in infancy. However, there is considerable heterogeneity in growth patterns that is obscured by simply analysing average growth trends, necessitating the analysis of growth in subpopulations.

Corrigendum: Systematic review on fiscal policy interventions in nutrition.

[This corrects the article DOI: 10.3389/fnut.2022.967494.].

Machine learning to attribute the source of Campylobacter infections in the United States: A retrospective analysis of national surveillance data.

OBJECTIVES: Integrating pathogen genomic surveillance with bioinformatics can enhance public health responses by identifying risk and guiding interventions. This study focusses on the two predominant Campylobacter species, which are commonly found in the gut of birds and mammals and often infect humans via contaminated food. Rising incidence and antimicrobial resistance (AMR) are a global concern, and there is an urgent need to quantify the main routes to human infection. METHODS: During routine US national surveillance (2009-2019), 8856 Campylobacter genomes from human infections and 16,703 from possible sources were sequenced. Using machine learning and probabilistic models, we target genetic variation associated with host adaptation to attribute the source of human infections and estimate the importance of different disease reservoirs. RESULTS: Poultry was identified as the primary source of human infections, responsible for an estimated 68% of cases, followed by cattle (28%), and only a small contribution from wild birds (3%) and pork sources (1%). There was also evidence of an increase in multidrug resistance, particularly among isolates attributed to chickens. CONCLUSIONS: National surveillance and source attribution can guide policy, and our study suggests that interventions targeting poultry will yield the greatest reductions in campylobacteriosis and spread of AMR in the US. DATA AVAILABILITY: All sequence reads were uploaded and shared on NCBI's Sequence Read Archive (SRA) associated with BioProjects; PRJNA239251 (CDC / PulseNet surveillance), PRJNA287430 (FSIS surveillance), PRJNA292668 & PRJNA292664 (NARMS) and PRJNA258022 (FDA surveillance). Publicly available genomes, including reference genomes and isolates sampled worldwide from wild birds are associated with BioProject accessions: PRJNA176480, PRJNA177352, PRJNA342755, PRJNA345429, PRJNA312235, PRJNA415188, PRJNA524300, PRJNA528879, PRJNA529798, PRJNA575343, PRJNA524315 and PRJNA689604. Contiguous assemblies of all genome sequences compared are available at Mendeley data (assembled C. coli genomes doi: 10.17632/gxswjvxyh3.1; assembled C. jejuni genomes doi: 10.17632/6ngsz3dtbd.1) and individual project and accession numbers can be found in Supplementary tables S1 and S2, which also includes pubMLST identifiers for assembled genomes. Figshare (10.6084/m9.figshare.20279928). Interactive phylogenies are hosted on microreact separately for C. jejuni (https://microreact.org/project/pascoe-us-cjejuni) and C. coli (https://microreact.org/project/pascoe-us-ccoli).

A Mixed Methods Exploration of the Role of Participation in a Nutrition-Sensitive Agroecology Intervention in Rural Tanzania.

Background: Participation is key to the successful implementation of nutrition-related interventions, but it has been relatively overlooked. Objective: We sought to describe participation intensity among smallholder farmers in a randomized nutrition-sensitive agroecology study in rural Tanzania. We explored the association between baseline characteristics and overall participation intensity (quantitatively at the individual level and qualitatively at the group level), the association of participation intensity with 2 process indicators, and the association between participation intensity and key study outcomes. Methods: Data came from 7 rounds of surveys with 295 women and 267 men across 29 months and 2 rounds of semi-structured interviews with the 20 "mentor farmers" who delivered the intervention. Participation intensity was based on the number of months of attendance at village-level project meetings or household visits (range: 0-29). Multivariable models of participation were built. Results: Women and men participated for 17.5 ± 7.2 and 13.6 ± 8.3 months, respectively. Participation intensity followed 1 latent trajectory: initially low, with a sharp increase after month 7, and plateaued after the first year. At baseline, higher participation intensity was associated with older age, higher education, level of women's empowerment, being in the middle quintile of wealth, and qualitatively, village residence. Higher participation intensity was associated with 2 process indicators - better recall of topics discussed during meetings and greater knowledge about key agroecological methods. High participation intensity was positively associated with increased use of sustainable agricultural practices among all participants, and among women, with husband's involvement in household tasks and child's dietary diversity score. Conclusions: Participation intensity covaried with key study outcomes, suggesting the value of increased attention to implementation in nutrition-related programs for providing insights into drivers of impact. We hope that investigations of participation, including participation intensity, will become more widespread so that intervention impacts, or lack thereof, can be better understood.

Rapid identification of enteric bacteria from whole genome sequences using average nucleotide identity metrics.

Identification of enteric bacteria species by whole genome sequence (WGS) analysis requires a rapid and an easily standardized approach. We leveraged the principles of average nucleotide identity using MUMmer (ANIm) software, which calculates the percent bases aligned between two bacterial genomes and their corresponding ANI values, to set threshold values for determining species consistent with the conventional identification methods of known species. The performance of species identification was evaluated using two datasets: the Reference Genome Dataset v2 (RGDv2), consisting of 43 enteric genome assemblies representing 32 species, and the Test Genome Dataset (TGDv1), comprising 454 genome assemblies which is designed to represent all species needed to query for identification, as well as rare and closely related species. The RGDv2 contains six Campylobacter spp., three Escherichia/Shigella spp., one Grimontia hollisae, six Listeria spp., one Photobacterium damselae, two Salmonella spp., and thirteen Vibrio spp., while the TGDv1 contains 454 enteric bacterial genomes representing 42 different species. The analysis showed that, when a standard minimum of 70% genome bases alignment existed, the ANI threshold values determined for these species were ≥95 for Escherichia/Shigella and Vibrio species, ≥93% for Salmonella species, and ≥92% for Campylobacter and Listeria species. Using these metrics, the RGDv2 accurately classified all validation strains in TGDv1 at the species level, which is consistent with the classification based on previous gold standard methods.

Synthesis of novel histamine H4 receptor antagonists.

This letter describes the discovery and synthesis of a series of octahydropyrrolo[3,4-c]pyrrole based selective histamine hH4 receptor antagonists. The amidine compound 20 was found to be a potent and selective histamine H4 receptor antagonist with moderate clearance and a high volume of distribution.

The discovery of UK-369003, a novel PDE5 inhibitor with the potential for oral bioavailability and dose-proportional pharmacokinetics.

This paper describes our recent efforts to design and synthesise potent and selective PDE5 inhibitors and the use of in vitro predictors of clearance, absorption and permeability to maximise the potential for dose-proportional pharmacokinetics and good oral bioavailability in man. Optimisation of the preclinical profile resulted in the identification of UK-369003 (19a) and its nomination as a clinical candidate. The clinical pharmacokinetic and safety profile has enabled us to progress the compound to test its efficacy in patients with lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) and a paper describing its efficacy has recently been published.

Making the most of existing research: an evidence gap map of the effects of food systems interventions in low-income and middle-income countries.

OBJECTIVE: Identify and describe the available evidence on the effects food systems interventions on food security and nutrition outcomes in low-income and middle-income countries. METHODS: An adapted version of the high-level panel of experts food systems framework defined the interventions and outcomes included studies. Included study designs were experimental and quasi-experimental quantitative impact evaluations and systematic reviews. Following standards for evidence gap maps developed by 3ie, a systematic search of 17 academic databases and 31 sector-specific repositories in May 2020 identified articles for inclusion. Trained consultants screened titles/abstracts, then full texts of identified articles. Studies meeting eligibility criteria had meta-data systematically extracted and were descriptively analysed. Systematic reviews were critically appraised. RESULTS: The map includes 1838 impact evaluations and 178 systematic reviews. The most common interventions, with over 100 impact evaluations and 20 systematic reviews each, were: provision of supplements, fortification, nutrition classes, direct provision of foods and peer support/counselling. Few studies addressed national-level interventions or women's empowerment. The most common final outcomes were: anthropometry, micronutrient status, and diet quality and adequacy. Intermediate outcomes were less studied.Most evaluations were conducted in sub-Saharan Africa (33%) or South Asia (20%). Many studies occurred in lower-middle-income countries (43%); few (7%) were in fragile countries. Among studies in a specific age group, infants were most frequently included (19%); 14% of these also considered mothers.Few evaluations considered qualitative or cost analysis; 75% used randomisation as the main identification strategy. DISCUSSION: The uneven distribution of research means that some interventions have established impacts while other interventions, often affecting large populations, are underevaluated. Areas for future research include the evaluation of national level policies, evaluation of efforts to support women's empowerment within the food system, and the synthesis of dietary quality. Quasi-experimental approaches should be adopted to evaluate difficult to randomise interventions.

Use of community engagement interventions to improve child immunisation in low-income and middle-income countries: a systematic review and meta-analysis.

OBJECTIVE: To support evidence informed decision-making, we systematically examine the effectiveness and cost-effectiveness of community engagement interventions on routine childhood immunisation outcomes in low-income and middle-income countries (LMICs) and identify contextual, design and implementation features associated with effectiveness. DESIGN: Mixed-methods systematic review and meta-analysis. DATA SOURCES: 21 databases of academic and grey literature and 12 additional websites were searched in May 2019 and May 2020. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: We included experimental and quasi-experimental impact evaluations of community engagement interventions considering outcomes related to routine child immunisation in LMICs. No language, publication type, or date restrictions were imposed. DATA EXTRACTION AND SYNTHESIS: Two independent researchers extracted summary data from published reports and appraised quantitative risk of bias using adapted Cochrane tools. Random effects meta-analysis was used to examine effects on the primary outcome, full immunisation coverage. RESULTS: Our search identified over 43 000 studies and 61 were eligible for analysis. The average pooled effect of community engagement interventions on full immunisation coverage was standardised mean difference 0.14 (95% CI 0.06 to 0.23, I2=94.46). The most common source of risk to the quality of evidence (risk of bias) was outcome reporting bias: most studies used caregiver-reported measures of vaccinations received by a child in the absence or incompleteness of immunisation cards. Reasons consistently cited for intervention success include appropriate intervention design, including building in community engagement features; addressing common contextual barriers of immunisation and leveraging facilitators; and accounting for existing implementation constraints. The median intervention cost per treated child per vaccine dose (excluding the cost of vaccines) to increase absolute immunisation coverage by one percent was US$3.68. CONCLUSION: Community engagement interventions are successful in improving outcomes related to routine child immunisation. The findings are robust to exclusion of studies assessed as high risk of bias.

Systematic review on fiscal policy interventions in nutrition.

Introduction: Both the World Health Organization and the Lancet Series on Adolescent nutrition recommend that governments adopt fiscal policies to combat diet-related non-communicable diseases (NCDs). However, rigorous, systematic evidence regarding the effects of these interventions is lacking. Methods: We synthesize the available evidence regarding the impacts of taxes and subsidies that directly affect consumer prices on availability and accessibility of foods and beverages, purchasing behavior, diet quality, health and well-being outcomes as well as considerations for implementation, sustainability and equity. Results: Our initial search returned 2,113 de-duplicated studies, and ultimately 24 impact evaluations and two systematic reviews met final eligibility criteria and represented unique evaluations. Our meta-analysis of these studies suggests that taxes may decrease purchases of taxed beverages (SMD = -0.14 [95% CI: -0.29 to -0.07], n = 15). Results should be interpreted cautiously due to considerable heterogeneity (Q(14) = 335.19, p = 0.01, τ ^ 2 = 0.03 , I 2 = 95.82%). Discussion: The evidence base is too limited to draw conclusions about the effects of taxes on beverages and calorie-dense foods on purchases, or on the effects of subsidies on purchasing or diet quality. Overall, the evidence base is inconclusive on whether fiscal policies can meaningfully influence the availability and accessibility of foods and beverages, diet quality, and health outcomes. Policymakers implementing fiscal policies should consider information campaigns on health benefits and health risks associated with certain food and beverage consumption. For taxes, exposure to health information may amplify signaling effects of taxes and reduce avoidance behaviors, such as cross-border shopping. Future evaluations should diversify data sources to better understand impacts on diet and health outcomes.

Use of community engagement interventions to improve child immunisation in low- and middle-income countries: A systematic review and meta-analysis.

Immunisation is one of the most cost-effective interventions to prevent and control life-threatening infectious diseases. Nonetheless, rates of routine vaccination of children in low- and middle-income countries (LMICs) are strikingly low or stagnant. In 2019, an estimated 19.7 million infants did not receive routine immunisations. Community engagement interventions are increasingly being emphasised in international and national policy frameworks as a means to improve immunisation coverage and reach marginalised communities. This systematic review examines the effectiveness and cost-effectiveness of community engagement interventions on outcomes related to childhood immunisation in LMICs and identifies contextual, design and implementation features that may be associated with effectiveness. We identified 61 quantitative and mixed methods impact evaluations and 47 associated qualitative studies related to community engagement interventions for inclusion in the reteview. For cost-effectiveness analysis 14 of the 61 studies had the needed combination of cost and effectiveness data. The 61 included impact evaluations were concentrated in South Asia and Sub-Saharan Africa and spread across 19 LMICs. The review found that community engagement interventions had a small but significant, positive effect on all primary immunisation outcomes related to coverage and their timeliness. The findings are robust to exclusion of studies assessed as high risk of bias. Qualitative evidence indicates appropriate intervention design, including building in community engagement features; addressing common contextual barriers of immunisation and leveraging facilitators; and accounting for existing implementation constraints and practicalities on the ground are consistently cited as reasons for intervention success. Among the studies for which we were able to calculate cost-effectiveness, we find that the median non-vaccine cost per dose of intervention to increase immunisation coverage by 1% was US $3.68. Given the broad scope of the review in terms of interventions and outcomes, there is significant variation in findings. Among the various types of community engagement interventions, those that involve creation of community buy-in or development of new cadres of community-based structures were found to have consistent positive effect on more primary vaccination coverage outcomes than if the engagement is limited to the design or delivery of an intervention or is a combination of the various types. The evidence base for sub-group analysis for female children was sparse (only two studies) and the effect on coverage of both full immunisation and third dose of diphtheria pertussis tetanus for this group was insignificant.

Challenges of drug discovery in novel target space. The discovery and evaluation of PF-3893787: a novel histamine H4 receptor antagonist.

We describe the development of novel benzimidazoles as small molecule histamine H4 receptor (H4R) antagonists and their profiling in rat early toxicity studies. The discovery and optimisation of a second series of pyrimidine based antagonists is then described culminating in the identification of the clinical development candidate 13 (PF-3893787). The pre-clinical profile of 13 (PF-3893787) is presented including the development of a translatable biomarker. Our pragmatic approach to target selection, safety assessment, and testing for efficacy faced numerous challenges and we share a number of lessons which the team learned and which will assist us and others in future drug discovery projects.

Discovery of a series of potent and selective human H4 antagonists using ligand efficiency and libraries to explore structure-activity relationship (SAR).

We describe the identification of a potent, selective lead series that shows antagonism against the human histamine H4 receptor from thirteen actives identified in an HTS as part of a hit to lead program. By focusing on ligand efficiency and concurrently using a diversity based approach, compounds based around 2,4-diaminopyrimidine were identified with compound 25 being quickly shown to be a good lead. It also had the highest ligand efficiency in the series.

Longitudinal interrelationship between HIV viral suppression, maternal weight change, breastfeeding, and length in HIV-exposed and uninfected infants participating in the Kabeho study in Kigali, Rwanda.

PURPOSE: The health of infants that are HIV-exposed and -uninfected (HEU) is a major public health concern as HIV becomes a chronic condition. We investigate the interrelationship between maternal viral suppression, maternal weight status, breastfeeding, and infants that are HEU. METHODS: The Kabeho study followed 502 HEU infants in Kigali, Rwanda, for 24 months from 2013 to 2014. We use a structural equation modeling approach to investigate the dynamic relationships between viral suppression, maternal weight change, breastfeeding, and infant length-for-age z-score (LAZ) as defined by the WHO. RESULTS: Older mothers are more likely to be virally suppressed and to breastfeed. Viral suppression and the mother being on antiretroviral treatment for longer were related to lower infant LAZ at three months. A more positive maternal weight change was related to higher infant LAZ at the end of each period. At 12 months, a higher infant LAZ was related to increased probability of continued breastfeeding. At 18 months, continued breastfeeding was related to lower LAZ, and food shortages were related to higher LAZ. CONCLUSION: There is a complex interrelationship between viral suppression, maternal weight change, breastfeeding, and infant LAZ. These relationships demonstrate the link between maternal and infant health in the context of HIV.

Ongoing Outbreak of Extensively Drug-Resistant Campylobacter jejuni Infections Associated With US Pet Store Puppies, 2016-2020.

Importance: Extensively drug-resistant Campylobacter jejuni infections cannot be treated with any commonly recommended antibiotics and pose an increasing public health threat. Objectives: To investigate cases of extensively drug-resistant C jejuni associated with pet store puppies and describe the epidemiologic and laboratory characteristics of these infections. Design, Setting, and Participants: In August 2017, health officials identified, via survey, patients with C jejuni infections who reported contact with puppies sold by pet stores. In conjunction with state and federal partners, the Centers for Disease Control and Prevention investigated cases of culture-confirmed C jejuni infections in US patients with an epidemiologic or molecular association with pet store puppies between January 1, 2016, and February 29, 2020. Available records from cases occurring before 2016 with genetically related isolates were also obtained. Main Outcomes and Measures: Patients were interviewed about demographic characteristics, health outcomes, and dog exposure during the 7 days before illness onset. Core genome multilocus sequence typing was used to assess isolate relatedness, and genomes were screened for resistance determinants to predict antibiotic resistance. Isolates resistant to fluoroquinolones, macrolides, and 3 or more additional antibiotic classes were considered to be extensively drug resistant. Cases before 2016 were identified by screening all sequenced isolates submitted for surveillance using core genome multilocus sequence typing. Results: A total of 168 patients (median [interquartile range] age, 37 [19.5-51.0] years; 105 of 163 female [64%]) with an epidemiologic or molecular association with pet store puppies were studied. A total of 137 cases occurred from January 1, 2016, to February 29, 2020, with 31 additional cases dating back to 2011. Overall, 117 of 121 patients (97%) reported contact with a dog in the week before symptom onset, of whom 69 of 78 (88%) with additional information reported contact with a pet store puppy; 168 isolates (88%) were extensively drug resistant. Traceback investigation did not implicate any particular breeder, transporter, distributer, store, or chain. Conclusions and Relevance: Strains of extensively drug-resistant C jejuni have been circulating since at least 2011 and are associated with illness among pet store customers, employees, and others who come into contact with pet store puppies. The results of this study suggest that practitioners should ask about puppy exposure when treating patients with Campylobacter infection, especially when they do not improve with routine antibiotics, and that the commercial dog industry should take action to help prevent the spread of extensively drug-resistant C jejuni from pet store puppies to people.

HIV-Exposed, Uninfected Infants in Uganda Experience Poorer Growth and Body Composition Trajectories than HIV-Unexposed Infants.

BACKGROUND: HIV-uninfected infants of HIV-positive women may experience worse growth and health outcomes than infants of HIV-negative women, but this has not been thoroughly investigated under the World Health Organization's most recent recommendations to reduce vertical transmission. OBJECTIVE: To determine whether HIV-exposed and -uninfected (HEU) infants whose mothers received Option B+ have higher odds of experiencing suboptimal growth trajectories than HIV-unexposed, -uninfected infants, and if this relationship is affected by food insecurity. DESIGN: Repeated anthropometric measures were taken on 238 infants (HEU = 86) at 1 week and 1, 3, 6, 9, and 12 months after delivery in Gulu, Uganda. Latent class growth mixture modeling was used to develop trajectories for length-for-age z-scores, weight-for-length z-scores, mid-upper arm circumference, sum of skinfolds, and arm fat area. Multinomial logistic models were also built to predict odds of trajectory class membership, controlling for socioeconomic factors. RESULTS: HEU infants had greater odds of being in the shortest 2 length-for-age z-scores trajectory classes [odds ratio (OR) = 3.80 (1.22-11.82), OR = 8.72 (1.80-42.09)] and higher odds of being in smallest sum of skinfolds trajectory class [OR = 3.85 (1.39-10.59)] vs. unexposed infants. Among HEU infants, increasing food insecurity was associated with lower odds of being in the lowest sum of skinfolds class [OR = 0.86 (0.76-0.98)]. CONCLUSIONS: There continues to be differences in growth patterns by HIV-exposure under the new set of World Health Organization guidelines for the prevention of mother-to-child transmission of HIV and the feeding of HEU infants in low-resource settings that are not readily identified through traditional mixed-effects modeling. Food insecurity was not associated with class membership, but differentially affected adiposity by HIV-exposure status.