Epidemiology and Treatment Outcomes of Tuberculosis With Chronic Hepatitis B Infection-California, 2016-2020.

BACKGROUND: Improved epidemiologic and treatment data for active tuberculosis (TB) with chronic hepatitis B virus (cHBV) infection might inform and encourage screening and vaccination programs focused on persons at risk of having both conditions. METHODS: We matched the California Department of Public Health TB registry during 2016-2020 to the cHBV registry using probabilistic matching algorithms. We used chi-square analysis to compare the characteristics of persons with TB and cHBV with those with TB only. We compared TB treatment outcomes between these groups using modified Poisson regression models. We calculated the time between reporting of TB and cHBV diagnoses for those with both conditions. RESULTS: We identified 8435 persons with TB, including 316 (3.7%) with cHBV. Among persons with TB and cHBV, 256 (81.0%) were non-US-born Asian versus 4186 (51.6%) with TB only (P < .0001). End-stage renal disease (26 [8.2%] vs 322 [4.0%]; P < .001) and HIV (21 [6.7%] vs 247 [3.0%]; P = .02) were more frequent among those with TB and cHBV compared with those with TB only. Among those with both conditions, 35 (11.1%) had TB diagnosed >60 days before cHBV (median, 363 days) and 220 (69.6%) had TB diagnosed >60 days after cHBV (median, 3411 days). CONCLUSIONS: Persons with TB and cHBV were found more frequently in certain groups compared with TB only, and infrequently had their conditions diagnosed together. This highlights an opportunity to improve screening and treatment of TB and cHBV in those at high risk for coinfection.

Expected vs Reported Chronic Hepatitis B Infection Cases in Persons with Active Tuberculosis - California, 2016-2020.

Epidemiologic data regarding persons with active tuberculosis (TB) and chronic hepatitis B virus (cHBV) infection are limited because of lack of routine surveillance of cHBV in persons with TB. Potential underdiagnosis of cHBV in California among those with TB is concerning. We matched TB and cHBV registries to identify cHBV infections among persons diagnosed with TB during 2016-2020 and described their demographic characteristics. We calculated expected cHBV cases among persons with TB for each demographic characteristic using published cHBV prevalence estimates for the locations of birth for persons with TB. Estimates were from general or emigrant adult and teen populations. Reported cHBV infection among persons with TB were 23% lower than expected, particularly among Asian persons, persons living in the two healthiest Healthy Places Index quartiles, and residents of less populated jurisdictions in California. Results show the possibility exists for underdiagnosis of cHBV in persons with TB in California.

The socioeconomic burden of pediatric tuberculosis and role of child-sensitive social protection.

BACKGROUND: Households of children with tuberculosis (TB) experience financial and social hardships, but TB-specific social protection initiatives primarily focus on adults. METHODS: We conducted a single-arm, pilot study of multi-component supportive benefits for children with pulmonary TB in Kampala, Uganda. At diagnosis, participants received in-kind coverage of direct medical costs, a cash transfer, and patient navigation. Caregivers were surveyed before diagnosis and 2 months into TB treatment on social and financial challenges related to their child's illness, including estimated costs, loss of income and dissaving practices. RESULTS: We included 368 children from 321 households. Pre-diagnosis, 80.1% of caregivers reported that their child's illness negatively impacted household finances, 44.1% of caregivers missed work, and 24% engaged in dissaving practices. Catastrophic costs (> 20% annual income) were experienced by 18.4% (95% CI 13.7-24.0) of households. School disruption was common (25.6%), and 28% of caregivers were concerned their child was falling behind in development. Two months post-diagnosis, 12 households (4.8%) reported being negatively affected by their child's TB disease (difference -75.2%, 95% CI -81.2 to -69.2, p < 0.001), with limited ongoing loss of income (1.6%) or dissavings practices (0.8%). Catastrophic costs occurred in one household (0.4%) at 2 months post-diagnosis. CONCLUSIONS: Households face financial and social challenges prior to a child's TB diagnosis, and child-sensitive social protection support may mitigate ongoing burden.

Epidemiology of Culture-Negative Pulmonary Tuberculosis-Alameda County, 2010-2019.

CONTEXT: Patients with culture-negative pulmonary TB (PTB) can face delays in diagnosis that worsen outcomes and lead to ongoing transmission. An understanding of current trends and characteristics of culture-negative PTB can support earlier detection and access to care. OBJECTIVE: Describe epidemiology of culture-negative PTB. DESIGN, SETTING, PARTICIPANTS: We utilized Alameda County TB surveillance data from 2010 to 2019. Culture-negative PTB cases met clinical but not laboratory criteria for PTB per US National Tuberculosis Surveillance System definitions. We calculated trends in annual incidence and proportion of culture-negative PTB using Poisson and weighted linear regression, respectively. We further compared demographic and clinical characteristics among culture-negative versus culture-positive PTB cases. RESULTS: During 2010-2019, there were 870 cases of PTB, of which 152 (17%) were culture-negative. The incidence of culture-negative PTB declined by 76%, from 1.9/100 000 to 0.46/100 000 ( P for trend <.01), while the incidence of culture-positive PTB reduced by 37% (6.5/100 000 to 4.1/100 000, P for trend =.1). Culture-negative PTB case-patients were more likely than culture-positive PTB case-patients to be younger (7.9% were children <15 years old vs 1.1%; P < .01), recent immigrants within 5 years of arrival (38.2% vs 25.5%; P < .01), and have a TB contact (11.2% vs 2.9%; P < .01). Culture-negative PTB case-patients were less likely than culture-positive PTB case-patients to be evaluated because of TB symptoms (57.2% vs 74.7%; P < .01) or have cavitation on chest imaging (13.1% vs 38.8%; P < .01). At the same time culture-negative PTB case-patients were less likely to die during TB treatment (2.0% vs 9.6%; P < .01). CONCLUSIONS: The incidence of culture-negative PTB disproportionately declined compared with culture-positive TB and raises concern for gaps in detection. Expansion of screening programs for recent immigrants and TB contacts and greater recognition of risk factors may increase detection of culture-negative PTB.

Engineered Electroactive Solutions for Electrochemical Detection of Tuberculosis-Associated Volatile Organic Biomarkers.

Rapid screening of tuberculosis by evaluation of associated volatile organic biomarkers in breath is a promising technology that is significantly faster and more convenient than traditional sputum culture tests. Methyl nicotinate (MN) and methyl p-anisate (MPA) have been isolated as potential biomarkers for mycobacterium tuberculosis and have been found in the breath of patients with active pulmonary tuberculosis. A novel approach to detection of these biomarkers in liquid droplets (e.g. from breath condensate) using inexpensive screen-printed electrodes is presented. Previous modelling studies suggest that these biomarkers complex with certain transition metals of particular valence state. This interaction can be exploited by mixing the biomarker sample into an electroactive solution (EAS) containing the functional metal ion and observing the change electrochemically. The study focuses on low biomarker concentrations, determined to be clinically relevant based on preliminary GC-MS studies of the levels found in patient breath. It was found that both the cyclic voltammogram and square wave voltammogram of copper(II) change significantly when as little as 0.1 mM MN is added to the solution, with analysis times of less than 2 min. Copper(II) exhibits three separate peaks during square wave voltammetry. The location and area of each peak are affected differently as the concentration of MN increases, suggesting a reaction with specific oxidation states of the metal. In this way, a "fingerprint" method can be used to identify biomarkers once their known interaction is established.

Toward Comprehensive Plasma Proteomics by Orthogonal Protease Digestion.

Rapid and consistent protein identification across large clinical cohorts is an important goal for clinical proteomics. With the development of data-independent technologies (DIA/SWATH-MS), it is now possible to analyze hundreds of samples with great reproducibility and quantitative accuracy. However, this technology benefits from empirically derived spectral libraries that define the detectable set of peptides and proteins. Here, we apply a simple and accessible tip-based workflow for the generation of spectral libraries to provide a comprehensive overview on the plasma proteome in individuals with and without active tuberculosis (TB). To boost protein coverage, we utilized nonconventional proteases such as GluC and AspN together with the gold standard trypsin, identifying more than 30,000 peptides mapping to 3309 proteins. Application of this library to quantify plasma proteome differences in TB infection recovered more than 400 proteins in 50 min of MS acquisition, including diagnostic Mycobacterium tuberculosis (Mtb) proteins that have previously been detectable primarily by antibody-based assays and intracellular proteins not previously described to be in plasma.

Outcomes of empiric treatment for pediatric tuberculosis, Kampala, Uganda, 2010-2015.

BACKGROUND: Childhood tuberculosis (TB) diagnoses often lack microbiologic confirmation and require empiric treatment. Barriers to empiric treatment include concern for poor outcomes and adverse effects. We thus determined the outcomes of empiric TB treatment from a retrospective cohort of children at a national referral hospital in Kampala, Uganda from 2010 to 2015. METHODS: Children were diagnosed clinically and followed through treatment. Demographics, clinical data, outcome and any adverse events were extracted from patient charts. A favorable outcome was defined as a child completing treatment with clinical improvement. We performed logistic regression to assess factors associated with loss to follow up and death. RESULTS: Of 516 children, median age was 36 months (IQR 15-73), 55% (95% CI 51-60%) were male, and HIV prevalence was 6% (95% CI 4-9%). The majority (n = 422, 82, 95% CI 78-85%) had a favorable outcome, with no adverse events that required treatment discontinuation. The most common unfavorable outcomes were loss to follow-up (57/94, 61%) and death (35/94, 37%; overall mortality 7%). In regression analysis, loss to follow up was associated with age 10-14 years (OR 2.38, 95% CI 1.15-4.93, p = 0.02), HIV positivity (OR 3.35, 95% CI 1.41-7.92, p = 0.01), hospitalization (OR 4.14, 95% CI 2.08-8.25, p < 0.001), and living outside of Kampala (OR 2.64, 95% CI 1.47-4.71, p = 0.001). Death was associated with hospitalization (OR 4.57, 95% CI 2.0-10.46, p < 0.001), severe malnutrition (OR 2.98, 95% CI 1.07-8.27, p = 0.04), baseline hepatomegaly (OR 4.11, 95% CI 2.09-8.09, p < 0.001), and living outside of Kampala (OR 2.41, 95% CI 1.17-4.96, p = 0.02). CONCLUSIONS: Empiric treatment of child TB was effective and safe, but treatment success remained below the 90% target. Addressing co-morbidities and improving retention in care may reduce unfavorable outcomes.

Desirability of Clinic-Based Financial Services in Urban Pediatric Primary Care.

OBJECTIVES: To determine the desirability of integrating financial services in pediatric primary care among caregivers and older adolescents. STUDY DESIGN: We conducted a cross-sectional study among caregivers and late adolescents 18 years and older attending an urban, pediatric primary care clinic. RESULTS: The 221 participants had a mean age of 32.1 years, with 28% of the sample aged 18-25 years. The majority were African American (90.1%), female (83.3%), and single parents (55.1%). More than one-third of the participants (35.8%) reported no household earned income, and 26.7% had a yearly household total income of <$12,000. More than one-half (61.5%) reported financial stress in general, and 67.9% believed that the clinic should provide financial services, including financial education and job workshops. A greater proportion of those who desired clinic-based services were African American (94.7% vs 75%; P < .001) and had a low or middle subjective social status (95.7% vs 83.7%; P = .01). CONCLUSIONS: Clinic-based financial services are desired by caregivers and late adolescents in an urban pediatric primary care practice. Prospective studies are needed to assess the long-term impact of integrated services on childhood poverty and family well-being.

Revisiting the mutant prevention concentration to guide dosing in childhood tuberculosis.

The mutant prevention concentration (MPC) is a well-known concept in the chemotherapy of many bacterial infections, but is seldom considered in relation to tuberculosis (TB) treatment, as the required concentrations are generally viewed as unachievable without undue toxicity. Early studies revealed single mutations conferring high MICs of first- and second-line anti-TB agents; however, the growing application of genomics and quantitative drug susceptibility testing in TB suggests a wide range of MICs often determined by specific mutations and strain type. In paediatric TB, pharmacokinetic studies indicate that despite increasing dose recommendations, a proportion of children still do not achieve adult-derived targets. When considering the next stage in anti-TB drug dosing and the introduction of novel therapies for children, we suggest consideration of MPC and its incorporation into pharmacokinetic studies to more accurately determine appropriate concentration targets in children, to restrict the growth of resistant mutants and better manage drug-resistant TB.

Urbanisation but not biomass fuel smoke exposure is associated with asthma prevalence in four resource-limited settings.

BACKGROUND: Urbanisation is an important contributor to the prevalence of asthma worldwide, and the burden of this effect in low-income and middle-income countries undergoing rapid industrialisation appears to be growing. We sought to characterise adult asthma prevalence across four geographically diverse settings in Peru and identify both individual and environmental risk factors associated with adult asthma. METHODS: We collected sociodemographics, clinical history and spirometry in adults aged ≥35 years. We defined asthma as meeting one of the three criteria: physician diagnosis, self-report of wheezing attack or use of asthma medications. We used multivariable logistic regression to assess individual and environmental factors associated with adult asthma. RESULTS: We analysed data from 2953 participants (mean age 55 years; 49% male). Overall asthma prevalence was 7.1%, which varied with urbanisation: highest in Lima (14.5%), followed by urban Puno (4.0%), semiurban Tumbes (3.8%) and rural Puno (1.8%). In multivariable analysis, being male (OR=0.60, 95% CI 0.39 to 0.93) and living at high altitude (OR=0.26, 95% CI 0.16 to 0.42) were associated with lower odds of having asthma, whereas living in an urban setting (OR=4.72, 95% CI 3.15 to 7.23) and family history of asthma (OR=1.83, 95% CI 1.19 to 2.73) were associated with higher odds. Current daily exposure to biomass fuel smoke (OR=1.18, 95% CI 0.70 to 1.91) and smoking (OR=0.99, 95% CI 0.73 to 1.22) were not associated with asthma. CONCLUSIONS: These findings confirm that urbanisation is an environmental risk factor of asthma, questions biomass fuel smoke exposure as an important risk factor and proposes high altitude as possibly protective against the development of asthma.

Modelling subject-specific childhood growth using linear mixed-effect models with cubic regression splines.

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 < 0.001) when using a linear mixed-effect models with random slopes and a first order continuous autoregressive error term. There was substantial heterogeneity in both the intercept (p < 0.001) and slopes (p < 0.001) of the individual growth trajectories. We also identified important serial correlation within the structure of the data (ρ = 0.66; 95 % CI 0.64 to 0.68; p < 0.001), which we modeled with a first order continuous autoregressive error term as evidenced by the variogram of the residuals and by a lack of association among residuals. The final model provides a parametric linear regression equation for both estimation and prediction of population- and individual-level growth in height. We show that cubic regression splines are superior to linear regression splines for the case of a small number of knots in both estimation and prediction with the full linear mixed effect model (AIC 19,352 vs. 19,598, respectively). While the regression parameters are more complex to interpret in the former, we argue that inference for any problem depends more on the estimated curve or differences in curves rather than the coefficients. Moreover, use of cubic regression splines provides biological meaningful growth velocity and acceleration curves despite increased complexity in coefficient interpretation. CONCLUSIONS: Through this stepwise approach, we provide a set of tools to model longitudinal childhood data for non-statisticians using linear mixed-effect models.

Urbanization and Daily Exposure to Biomass Fuel Smoke Both Contribute to Chronic Bronchitis Risk in a Population with Low Prevalence of Daily Tobacco Smoking.

OBJECTIVE: Risk factors beyond tobacco smoking associated with chronic bronchitis are not well understood. We sought to describe the prevalence and risk factors of chronic bronchitis across four distinct settings in Peru with overall low prevalence of tobacco smoking yet varying degrees of urbanization, daily exposure to biomass fuel smoke and living at high altitude. METHODS: We analyzed data of 2,947 participants from rural and urban Puno, Lima and Tumbes including spirometry, blood samples, anthropometry and administered questionnaires about respiratory symptoms. We used multivariable Poisson regression to assess biologic, socioeconomic and environmental risk factors associated with chronic bronchitis. RESULTS: Overall prevalence of chronic bronchitis was 5.9% (95%CI 5.1%-6.9%) with variation by setting: prevalence was lower in semi-urban Tumbes (1.3%) vs. highly urbanized Lima (8.9%), urban Puno (7.0%) and rural Puno (7.8%; p < 0.001). Chronic bronchitis was more common among participants with vs. without COPD based on FEV1/FVC< LLN (12.1% vs 5.6%, p < 0.01) and it was associated with increased reporting of dyspnea on exertion (p < 0.001), hospitalization (p = 0.003) and workdays missed due to respiratory symptoms (p < 0.001). Older age (Prevalence ratio [PR] = 1.23 for each 10-years of age, 95%CI 1.09-1.40) past history of asthma (PR = 2.87, 95%CI 1.80-4.56), urbanization (PR = 3.34, 95%CI 2.18-5.11) and daily exposure to biomass fuel smoke (PR = 2.00, 95%CI 1.30-3.07) were all associated with chronic bronchitis. CONCLUSIONS: We found important variations in the prevalence of chronic bronchitis across settings. Prevalence increased with both urbanization and with daily exposure to biomass fuel smoke. Having chronic bronchitis was also associated with worse patient-centered outcomes including dyspnea, hospitalization and missed workdays.

The role of pre-primary classes on school-age cognition in rural Nepal.

OBJECTIVES: In rural Nepal, we assessed the factors associated with pre-primary school attendance and its relationship to cognitive testing and school progress. STUDY DESIGN: Sociodemographic, household, and schooling data were collected among 1466 children age 7-9 years from Sarlahi, Nepal. We performed the Universal Nonverbal Intelligence Test, backward digit span, go/no-go test, Movement Assessment Battery for Children, finger-tapping test, and Stroop numbers test. We conducted adjusted regression analyses to determine the association of pre-primary school attendance with test results and school progress. RESULTS: We found that pre-primary class enrollment was lower among children of female sex, Madheshi ethnicity, and low socioeconomic status. In adjusted analyses, pre-primary school enrollment was associated with beneficial scores on all cognitive tests. In addition, children who attended pre-primary school were less likely to repeat grade 1 (prevalence ratio 0.15, 95% CI 0.08-0.30, P < .001) or ever fail a grade (prevalence ratio 0.48, 95% CI 0.26-0.90, P = .02). CONCLUSIONS: In rural Nepal, there continue to be disparities in pre-primary school attendance; however, independent of these factors, pre-primary school attendance was associated with benefits in multiple cognitive domains and early school performance.

Prevalence of chronic obstructive pulmonary disease and variation in risk factors across four geographically diverse resource-limited settings in Peru.

BACKGROUND: It is unclear how geographic and social diversity affects the prevalence of chronic obstructive pulmonary disease (COPD). We sought to characterize the prevalence of COPD and identify risk factors across four settings in Peru with varying degrees of urbanization, altitude, and biomass fuel use. METHODS: We collected sociodemographics, clinical history, and post-bronchodilator spirometry in a randomly selected, age-, sex- and site-stratified, population-based sample of 2,957 adults aged ≥35 years (median age was 54.8 years and 49.3% were men) from four resource-poor settings: Lima, Tumbes, urban and rural Puno. We defined COPD as a post-bronchodilator FEV1/FVC < 70%. RESULTS: Overall prevalence of COPD was 6.0% (95% CI 5.1%-6.8%) but with marked variation across sites: 3.6% in semi-urban Tumbes, 6.1% in urban Puno, 6.2% in Lima, and 9.9% in rural Puno (p < 0.001). Population attributable risks (PARs) of COPD due to smoking ≥10 pack-years were less than 10% for all sites, consistent with a low prevalence of daily smoking (3.3%). Rather, we found that PARs of COPD varied by setting. In Lima, for example, the highest PARs were attributed to post-treatment tuberculosis (16% and 22% for men and women, respectively). In rural Puno, daily biomass fuel for cooking among women was associated with COPD (prevalence ratio 2.22, 95% CI 1.02-4.81) and the PAR of COPD due to daily exposure to biomass fuel smoke was 55%. CONCLUSIONS: The burden of COPD in Peru was not uniform and, unlike other settings, was not predominantly explained by tobacco smoking. This study emphasizes the role of biomass fuel use, and highlights pulmonary tuberculosis as an often neglected risk factor in endemic areas.

Sleep deprivation impairs cAMP signalling in the hippocampus.

Millions of people regularly obtain insufficient sleep. Given the effect of sleep deprivation on our lives, understanding the cellular and molecular pathways affected by sleep deprivation is clearly of social and clinical importance. One of the major effects of sleep deprivation on the brain is to produce memory deficits in learning models that are dependent on the hippocampus. Here we have identified a molecular mechanism by which brief sleep deprivation alters hippocampal function. Sleep deprivation selectively impaired 3', 5'-cyclic AMP (cAMP)- and protein kinase A (PKA)-dependent forms of synaptic plasticity in the mouse hippocampus, reduced cAMP signalling, and increased activity and protein levels of phosphodiesterase 4 (PDE4), an enzyme that degrades cAMP. Treatment of mice with phosphodiesterase inhibitors rescued the sleep-deprivation-induced deficits in cAMP signalling, synaptic plasticity and hippocampus-dependent memory. These findings demonstrate that brief sleep deprivation disrupts hippocampal function by interfering with cAMP signalling through increased PDE4 activity. Thus, drugs that enhance cAMP signalling may provide a new therapeutic approach to counteract the cognitive effects of sleep deprivation.

Distribution and transmission of Mycobacterium tuberculosis complex lineages among children in peri-urban Kampala, Uganda.

BACKGROUND: To gain insight into the transmission of tuberculosis (TB) in peri-urban Kampala-Uganda, we performed a household contact study using children as a surrogate for recent transmission of Mycobacterium tuberculosis (MTB). Using this approach, we sought to understand M. tuberculosis complex (MTBC) lineage diversity, distribution and how these relate to TB transmission to exposed children. METHOD: MTBC isolates from children aged ≤ 15 years, collected from 2002 to 2010 in a household-contact study, were analyzed using a LightCycler RT-PCR SNP genotyping assay (LRPS). The resultant genotypic data was used to determine associations between MTBC lineage and the children's clinical and epidemiological characteristics. RESULTS AND DISCUSSION: Of the 761 children surveyed, 9% (69/761) had culture-positive TB an estimate in the range of global childhood TB; of these 71% (49/69) were infected with an MTBC strain of the "Uganda family", 17% (12/69) infected with MTBC lineage 4 strains other than MTBC Uganda family and 12% (8/69) infected with MTBC lineage 3, thereby disproportionately causing TB in the study area. Overall the data showed no correlation between the MTBC lineages studied and transmission (OR = 0.304; P-value = 0.251; CI: 95%; 0.039-2.326) using children a proxy for TB transmission. CONCLUSIONS: Our findings indicate that MTBC Uganda family strains are the main cause of TB in children in peri-urban Kampala. Furthermore, MTBC lineages did not differ in their transmissibility to children.

Project HOPE: online social network changes in an HIV prevention randomized controlled trial for African American and Latino men who have sex with men.

OBJECTIVES: We examined whether and how an HIV prevention diffusion-based intervention spread throughout participants' online social networks and whether changes in social network ties were associated with increased HIV prevention and testing behaviors. METHODS: We randomly assigned 112 primarily racial/ethnic minority men who have sex with men (MSM) to receive peer-delivered HIV (intervention) or general health (control) information over 12 weeks through closed Facebook groups. We recorded participants' public Facebook friend networks at baseline (September 2010) and follow-up (February 2011), and assessed whether changes in network growth were associated with changes in health engagement and HIV testing. RESULTS: Within-group ties increased in both conditions from baseline to follow-up. Among the intervention group, we found a significant positive relation between increased network ties and using social media to discuss sexual behaviors. We found a positive trending relationship between increased network ties and likelihood of HIV testing, follow-up for test results, and participation in online community discussions. No significant differences were seen within control groups. CONCLUSIONS: Among high-risk MSM, peer-led social media HIV prevention interventions can increase community cohesion. These changes appear to be associated with increased HIV prevention and testing behaviors.

First detected Helicobacter pylori infection in infancy modifies the association between diarrheal disease and childhood growth in Peru.

BACKGROUND: In endemic settings, Helicobacter pylori infection can occur shortly after birth and may be associated with a reduction in childhood growth. MATERIALS AND METHODS: This study investigated what factors promote earlier age of first H. pylori infection and evaluated the role of H. pylori infection in infancy (6-11 months) versus early childhood (12-23 months) on height. We included 183 children near birth from a peri-urban shanty town outside of Lima, Peru. Field-workers collected data on socioeconomic status (SES), daily diarrheal and breast-feeding history, antibiotic use, anthropometrics, and H. pylori status via carbon 13-labeled urea breath test up to 24 months after birth. We used a proportional hazards model to assess risk factors for earlier age at first detected infection and linear mixed-effects models to evaluate the association of first detected H. pylori infection during infancy on attained height. RESULTS: One hundred and forty (77%) were infected before 12 months of age. Lower SES was associated with earlier age at first detected H. pylori infection (low vs middle-to-high SES Hazard ratio (HR) 1.59, 95% CI 1.16, 2.19; p = .004), and greater exclusive breast-feeding was associated with reduced likelihood (HR 0.63, 95% CI 0.40, 0.98, p = .04). H. pylori infection in infancy was not independently associated with growth deficits (p = .58). However, children who had their first detected H. pylori infection in infancy (6-11 months) versus early childhood (12-23 months) and who had an average number of diarrhea episodes per year (3.4) were significantly shorter at 24 months (-0.37 cm, 95% CI, -0.60, -0.15 cm; p = .001). DISCUSSION: Lower SES was associated with a higher risk of first detected H. pylori infection during infancy, which in turn augmented the adverse association of diarrheal disease on linear growth.