Robert H Gilman’s research while affiliated with Johns Hopkins University and other places

Helicobacter pylori , a dominant member of the gastric microbiota, shares co-evolutionary history with humans. This has led to the development of genetically distinct H. pylori subpopulations associated with the geographic origin of the host and with differential gastric disease risk. Here, we provide insights into H. pylori population structure as a part of the Helicobacter pylori Genome Project ( Hp GP), a multi-disciplinary initiative aimed at elucidating H. pylori pathogenesis and identifying new therapeutic targets. We collected 1011 well-characterized clinical strains from 50 countries and generated high-quality genome sequences. We analysed core genome diversity and population structure of the Hp GP dataset and 255 worldwide reference genomes to outline the ancestral contribution to Eurasian, African, and American populations. We found evidence of substantial contribution of population hpNorthAsia and subpopulation hspUral in Northern European H. pylori . The genomes of H. pylori isolated from northern and southern Indigenous Americans differed in that bacteria isolated in northern Indigenous communities were more similar to North Asian H. pylori while the southern had higher relatedness to hpEastAsia. Notably, we also found a highly clonal yet geographically dispersed North American subpopulation, which is negative for the cag pathogenicity island, and present in 7% of sequenced US genomes. We expect the Hp GP dataset and the corresponding strains to become a major asset for H. pylori genomics.

Sustainable Development Goal 2.2—to end malnutrition by 2030—includes the elimination of child wasting, defined as a weight-for-length z -score that is more than two standard deviations below the median of the World Health Organization standards for child growth ¹ . Prevailing methods to measure wasting rely on cross-sectional surveys that cannot measure onset, recovery and persistence—key features that inform preventive interventions and estimates of disease burden. Here we analyse 21 longitudinal cohorts and show that wasting is a highly dynamic process of onset and recovery, with incidence peaking between birth and 3 months. Many more children experience an episode of wasting at some point during their first 24 months than prevalent cases at a single point in time suggest. For example, at the age of 24 months, 5.6% of children were wasted, but by the same age (24 months), 29.2% of children had experienced at least one wasting episode and 10.0% had experienced two or more episodes. Children who were wasted before the age of 6 months had a faster recovery and shorter episodes than did children who were wasted at older ages; however, early wasting increased the risk of later growth faltering, including concurrent wasting and stunting (low length-for-age z -score), and thus increased the risk of mortality. In diverse populations with high seasonal rainfall, the population average weight-for-length z -score varied substantially (more than 0.5 z in some cohorts), with the lowest mean z -scores occurring during the rainiest months; this indicates that seasonally targeted interventions could be considered. Our results show the importance of establishing interventions to prevent wasting from birth to the age of 6 months, probably through improved maternal nutrition, to complement current programmes that focus on children aged 6–59 months.

Growth faltering in children (low length for age or low weight for length) during the first 1,000 days of life (from conception to 2 years of age) influences short-term and long-term health and survival 1,2 . Interventions such as nutritional supplementation during pregnancy and the postnatal period could help prevent growth faltering, but programmatic action has been insufficient to eliminate the high burden of stunting and wasting in low- and middle-income countries. Identification of age windows and population subgroups on which to focus will benefit future preventive efforts. Here we use a population intervention effects analysis of 33 longitudinal cohorts (83,671 children, 662,763 measurements) and 30 separate exposures to show that improving maternal anthropometry and child condition at birth accounted for population increases in length-for-age z -scores of up to 0.40 and weight-for-length z -scores of up to 0.15 by 24 months of age. Boys had consistently higher risk of all forms of growth faltering than girls. Early postnatal growth faltering predisposed children to subsequent and persistent growth faltering. Children with multiple growth deficits exhibited higher mortality rates from birth to 2 years of age than children without growth deficits (hazard ratios 1.9 to 8.7). The importance of prenatal causes and severe consequences for children who experienced early growth faltering support a focus on pre-conception and pregnancy as a key opportunity for new preventive interventions.

Globally, 149 million children under 5 years of age are estimated to be stunted (length more than 2 standard deviations below international growth standards) 1,2 . Stunting, a form of linear growth faltering, increases the risk of illness, impaired cognitive development and mortality. Global stunting estimates rely on cross-sectional surveys, which cannot provide direct information about the timing of onset or persistence of growth faltering—a key consideration for defining critical windows to deliver preventive interventions. Here we completed a pooled analysis of longitudinal studies in low- and middle-income countries ( n = 32 cohorts, 52,640 children, ages 0–24 months), allowing us to identify the typical age of onset of linear growth faltering and to investigate recurrent faltering in early life. The highest incidence of stunting onset occurred from birth to the age of 3 months, with substantially higher stunting at birth in South Asia. From 0 to 15 months, stunting reversal was rare; children who reversed their stunting status frequently relapsed, and relapse rates were substantially higher among children born stunted. Early onset and low reversal rates suggest that improving children’s linear growth will require life course interventions for women of childbearing age and a greater emphasis on interventions for children under 6 months of age.

This cross-sectional study estimated a one-time point seroprevalence rate of Chagas disease among people of Latin American descent in Suffolk County, Long Island, New York. Subjects who met the inclusion criteria were screened using the Chagas Detect Plus Rapid Test (InBios, Seattle, WA) with confirmation via Trypanosoma cruzi enzyme immunoassay and T. cruzi immunoblot assay. Administration of a questionnaire regarding demographics and risk factors followed. A seroprevalence rate of 10.74% was found. Identified risk factors included prior residence in a palm leaf house (odds ratio [OR], 10.42; P = 0.003; 95% CI, 2.18–49.76), residence in a house with triatomines (OR, 9.03; P = 0.006; 95% CI, 1.90–42.88), and history of triatomine bite (OR, 9.52; P = 0.009; 95% CI, 1.75–51.77). Our findings emphasize the importance of this frequently underdiagnosed disease and help highlight the importance of early screening among high-risk populations.

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.

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.