Different Clinical Presentations of Human Rhinovirus Species Infection in Children and Adults in Mexico.

Background: Human rhinoviruses (HRVs) are a common cause of influenza-like illness, with the ability to infect the upper and lower respiratory tracts. In this study we aim to describe the clinical and molecular features of HRV infection in Mexican children and adults. Methods: We performed a hospital-based, 4-year multicenter prospective observational cohort study of patients with influenza-like illness. Participants who tested positive for HRV were included. We described demographic, clinical, and laboratory characteristics and the association between HRV types, illness severity, and clinical outcomes. Results: Of the 5662 subjects recruited, 1473 (26%) had HRV; of those, 988 (67.1%) were adults (≥18 years) and 485 (32.9%) were children. One hundred sixty-seven (11.33%) samples were sequenced; 101 (60.5%) were rhinovirus species A (HRV-A), 22 (13.2%) were rhinovirus species B (HRV-B), and 44 (26.3%) were rhinovirus species C (HRV-C). Among children and adults, 30.5% and 23.5%, respectively, were hospitalized (non-intensive care unit [ICU]). The odds of HRV-C are higher than HRV-A for participants in the ICU (compared to outpatient) and when platelets, lymphocytes, white blood cells, and lactate dehydrogenase are increased. The odds of HRV-C are higher than HRV-A and HRV-B with shortness of breath. The odds of HRV-A are higher than HRV-B, and the odds of HRV-B are higher than HRV-C, when mild symptoms like muscle ache and headache occur. Conclusions: Rhinoviruses are a common cause of influenza-like illness. It is necessary to improve the surveillance, testing, and species identification for these viruses to understand different clinical presentations and risk factors associated with worse outcomes. Clinical Trials Registration. NCT01418287.

Comparison of Rates of Hospitalization Between Single and Dual Virus Detection in a Mexican Cohort of Children and Adults With Influenza-Like Illness.

BACKGROUND: Molecular detection methods allow for the simultaneous detection of several infectious agents. This study assesses whether co-infection with 2 viruses as compared with 1 is associated with increased hospitalization in those with acute respiratory infections. METHODS: We prospectively enrolled a cohort of pediatric and adult participants with influenza-like illness during 2010-2014 in Mexico. Clinical information and respiratory samples were collected at enrollment. Respiratory viruses were detected with multiplex polymerase chain reaction (PCR) and influenza-specific reverse transcription PCR assays. Participants were followed for 14 and 28 days after inclusion. Severity of disease, as measured by hospitalization with acute respiratory infections, was compared between single and dual viral infections. RESULTS: Among 5662 participants in the study, either 1 (n = 3285) or 2 (n = 641) viruses were detected in 3926 participants. Rhinovirus (n = 1433), influenza (n = 888), and coronaviruses (n = 703) were the most frequently detected viruses (either alone or in co-infection). Bocavirus, respiratory syncytial virus (RSV), metapneumovirus, and rhinovirus cases were hospitalized more often than other viruses. Bocavirus+rhinovirus cases were hospitalized more often than those with rhinovirus alone (but not bocavirus alone). RSV cases were more likely to be hospitalized than cases with co-infections of RSV and parainfluenza virus or coronavirus. Metapneumovirus cases were hospitalized more often than those co-infected with metapneumovirus+coronavirus. CONCLUSIONS: In this study, detection of 2 viruses did not significantly increase hospitalizations compared with single virus infections. Larger studies will allow for distinguishing between sequential and simultaneous infection and for a better understanding of the role of each virus during the evolution of acute respiratory episodes.

Heterogeneous susceptibility to rotavirus infection and gastroenteritis in two birth cohort studies: Parameter estimation and epidemiological implications.

Cohort studies, randomized trials, and post-licensure studies have reported reduced natural and vaccine-derived protection against rotavirus gastroenteritis (RVGE) in low- and middle-income countries. While susceptibility of children to rotavirus is known to vary within and between settings, implications for estimation of immune protection are not well understood. We sought to re-estimate naturally-acquired protection against rotavirus infection and RVGE, and to understand how differences in susceptibility among children impacted estimates. We re-analyzed data from studies conducted in Mexico City, Mexico and Vellore, India. Cumulatively, 573 rotavirus-unvaccinated children experienced 1418 rotavirus infections and 371 episodes of RVGE over 17,636 child-months. We developed a model that characterized susceptibility to rotavirus infection and RVGE among children, accounting for aspects of the natural history of rotavirus and differences in transmission rates between settings. We tested whether model-generated susceptibility measurements were associated with demographic and anthropometric factors, and with the severity of RVGE symptoms. We identified greater variation in susceptibility to rotavirus infection and RVGE in Vellore than in Mexico City. In both cohorts, susceptibility to rotavirus infection and RVGE were associated with male sex, lower birth weight, lower maternal education, and having fewer siblings; within Vellore, susceptibility was also associated with lower socioeconomic status. Children who were more susceptible to rotavirus also experienced higher rates of rotavirus-negative diarrhea, and higher risk of moderate-to-severe symptoms when experiencing RVGE. Simulations suggested that discrepant estimates of naturally-acquired immunity against RVGE can be attributed, in part, to between-setting differences in susceptibility of children, but result primarily from the interaction of transmission rates with age-dependent risk for infections to cause RVGE. We found that more children in Vellore than in Mexico City belong to a high-risk group for rotavirus infection and RVGE, and demonstrate that unmeasured individual- and age-dependent susceptibility may influence estimates of naturally-acquired immune protection against RVGE.

Efficacy and Safety of Nitazoxanide in Addition to Standard of Care for the Treatment of Severe Acute Respiratory Illness.

BACKGROUND: Effective therapeutics for respiratory viruses are needed. Early data suggest that nitazoxanide (NTZ) may be beneficial for treating acute respiratory viral illness. METHODS: From March 2014 through March 2017, a double-blind, placebo-controlled trial was conducted in 260 participants ≥1 year old hospitalized with influenza-like illness at 6 hospitals in Mexico. Participants were randomized 1:1 to NTZ (age ≥12 years, 600 mg twice daily; age 4-11 years and 1-3 years, 200 or 100 mg twice daily, respectively) or placebo for 5 days in addition to standard of care. The primary endpoint was time from first dose to hospital discharge. Influenza reverse-transcription polymerase chain reaction and Respifinder 22 multiplex test were used for virus detection. RESULTS: Of 260 participants enrolled, 257 were randomized and took at least 1 dose of study treatment (intention-to-treat population): 130 in the NTZ group and 127 in the placebo group. The Kaplan-Meier estimate of the median duration of hospitalization was 6.5 (interquartile range [IQR], 4.0-9.0) days in the NTZ group vs 7.0 (IQR, 4.0-9.0) days in the placebo group (P = .56). Duration of hospitalization between the 2 treatments was similar in children (P = .29) and adults (P = .62), influenza A and B (P = .32), and other respiratory viruses. Seven (5.4%) and 6 (4.7%) participants in the NTZ and placebo groups, respectively, reported serious adverse events. CONCLUSIONS: Treatment with NTZ did not reduce the duration of hospital stay in severe influenza-like illness. Further analyses based on age and evaluations by virus did not reveal any subgroups that appeared to benefit from NTZ. CLINICAL TRIALS REGISTRATION: NCT02057757.

Performance of the inFLUenza Patient-Reported Outcome (FLU-PRO) diary in patients with influenza-like illness (ILI).

BACKGROUND: The inFLUenza Patient Reported Outcome (FLU-PRO) measure is a daily diary assessing signs/symptoms of influenza across six body systems: Nose, Throat, Eyes, Chest/Respiratory, Gastrointestinal, Body/Systemic, developed and tested in adults with influenza. OBJECTIVES: This study tested the reliability, validity, and responsiveness of FLU-PRO scores in adults with influenza-like illness (ILI). METHODS: Data from the prospective, observational study used to develop and test the FLU-PRO in influenza virus positive patients were analyzed. Adults (≥18 years) presenting with influenza symptoms in outpatient settings in the US, UK, Mexico, and South America were enrolled, tested for influenza virus, and asked to complete the 37-item draft FLU-PRO daily for up to 14-days. Analyses were performed on data from patients testing negative. Reliability of the final, 32-item FLU-PRO was estimated using Cronbach's alpha (α; Day 1) and intraclass correlation coefficients (ICC; 2-day reproducibility). Convergent and known-groups validity were assessed using patient global assessments of influenza severity (PGA). Patient report of return to usual health was used to assess responsiveness (Day 1-7). RESULTS: The analytical sample included 220 ILI patients (mean age = 39.3, 64.1% female, 88.6% white). Sixty-one (28%) were hospitalized at some point in their illness. Internal consistency reliability (α) of FLU-PRO Total score was 0.90 and ranged from 0.72-0.86 for domain scores. Reproducibility (Day 1-2) was 0.64 for Total, ranging from 0.46-0.78 for domain scores. Day 1 FLU-PRO scores correlated (≥0.30) with the PGA (except Gastrointestinal) and were significantly different across PGA severity groups (Total: F = 81.7, p<0.001; subscales: F = 6.9-62.2; p<0.01). Mean score improvements Day 1-7 were significantly greater in patients reporting return to usual health compared with those who did not (p<0.05, Total and subscales, except Gastrointestinal and Eyes). CONCLUSIONS: Results suggest FLU-PRO scores are reliable, valid, and responsive in adults with influenza-like illness.

Reliability, Validity, and Responsiveness of InFLUenza Patient-Reported Outcome (FLU-PRO©) Scores in Influenza-Positive Patients.

OBJECTIVES: To assess the reliability, validity, and responsiveness of InFLUenza Patient-Reported Outcome (FLU-PRO©) scores for quantifying the presence and severity of influenza symptoms. METHODS: An observational prospective cohort study of adults (≥18 years) with influenza-like illness in the United States, the United Kingdom, Mexico, and South America was conducted. Participants completed the 37-item draft FLU-PRO daily for up to 14 days. Item-level and factor analyses were used to remove items and determine factor structure. Reliability of the final tool was estimated using Cronbach α and intraclass correlation coefficients (2-day reliability). Convergent and known-groups validity and responsiveness were assessed using global assessments of influenza severity and return to usual health. RESULTS: Of the 536 patients enrolled, 221 influenza-positive subjects comprised the analytical sample. The mean age of the patients was 40.7 years, 60.2% were women, and 59.7% were white. The final 32-item measure has six factors/domains (nose, throat, eyes, chest/respiratory, gastrointestinal, and body/systemic), with a higher order factor representing symptom severity overall (comparative fit index = 0.92; root mean square error of approximation = 0.06). Cronbach α was high (total = 0.92; domain range = 0.71-0.87); test-retest reliability (intraclass correlation coefficient, day 1-day 2) was 0.83 for total scores and 0.57 to 0.79 for domains. Day 1 FLU-PRO domain and total scores were moderately to highly correlated (≥0.30) with Patient Global Rating of Flu Severity (except nose and throat). Consistent with known-groups validity, scores differentiated severity groups on the basis of global rating (total: F = 57.2, P < 0.001; domains: F = 8.9-67.5, P < 0.001). Subjects reporting return to usual health showed significantly greater (P < 0.05) FLU-PRO score improvement by day 7 than did those who did not, suggesting score responsiveness. CONCLUSIONS: Results suggest that FLU-PRO scores are reliable, valid, and responsive to change in influenza-positive adults.

Naturally Acquired Immunity Against Rotavirus Infection and Gastroenteritis in Children: Paired Reanalyses of Birth Cohort Studies.

Background: Observational studies in socioeconomically distinct populations have yielded conflicting conclusions about the strength of naturally acquired immunity against rotavirus gastroenteritis (RVGE), mirroring vaccine underperformance in low-income countries. We revisited birth cohort studies to understand naturally acquired protection against rotavirus infection and RVGE. Methods: We reanalyzed data from 200 Mexican and 373 Indian children followed from birth to 2 and 3 years of age, respectively. We reassessed protection against RVGE, decomposing the incidence rate into the rate of rotavirus infection and the risk of RVGE given infection, and tested for serum antibody correlates of protection using regression models. Results: Risk for primary, secondary, and subsequent infections to cause RVGE decreased per log-month of age by 28% (95% confidence interval [CI], 12%-41%), 69% (95% CI, 30%-86%), and 64% (95% CI, -186% to 95%), respectively, in Mexico City, and by 10% (95% CI, -1% to 19%), 51% (95% CI, 41%-59%) and 67% (95% CI, 57%-75%), respectively, in Vellore. Elevated serum immunoglobulin A and immunoglobulin G titers were associated with partial protection against rotavirus infection. Associations between older age and reduced risk for RVGE or moderate-to-severe RVGE given infection persisted after controlling for antibody levels. Conclusions: Dissimilar estimates of protection against RVGE may be due in part to age-related, antibody-independent risk for rotavirus infections to cause RVGE.

Epidemiology and clinical characteristics of respiratory syncytial virus infections among children and adults in Mexico.

BACKGROUND: Respiratory syncytial virus (RSV) is a leading etiological agent of acute respiratory tract infections and hospitalizations in children. However, little information is available regarding RSV infections in Latin American countries, particularly among adult patients. OBJECTIVE: To describe the epidemiology of RSV infection and to analyze the factors associated with severe infections in children and adults in Mexico. METHODS: Patients ≥1 month old, who presented with an influenza-like illness (ILI) to six hospitals in Mexico, were eligible for participation in the study. Multiplex reverse-transcriptase polymerase chain reaction identified viral pathogens in nasal swabs from 5629 episodes of ILI. Patients in whom RSV was detected were included in this report. RESULTS: Respiratory syncytial virus was detected in 399 children and 171 adults. RSV A was detected in 413 cases and RSV B in 163, including six patients who had coinfection with both subtypes; 414 (72.6%) patients required hospital admission, including 96 (16.8%) patients that required admission to the intensive care unit. Coinfection with one or more respiratory pathogens other than RSV was detected in 159 cases. Young age (in children) and older age (in adults) as well as the presence of some underlying conditions were associated with more severe disease. CONCLUSIONS: This study confirms that RSV is an important respiratory pathogen in children in Mexico. In addition, a substantial number of cases in adults were also detected highlighting the relevance of this virus in all ages. It is important to identify subjects at high risk of complications who may benefit from current or future preventive interventions.

Branched-chain fatty acid composition of human milk and the impact of maternal diet: the Global Exploration of Human Milk (GEHM) Study.

BACKGROUND: An understudied component of the diet, branched-chain fatty acids (BCFAs) are distinctive saturated fatty acids that may have an important influence on health. Human-milk fatty acid composition is known to differ worldwide, but comparative data are lacking on BCFAs. OBJECTIVE: We tested the hypotheses that concentrations of BCFAs in human milk differ between populations and are associated with maternal diet. DESIGN: We surveyed the BCFA composition of samples collected as part of a standardized, prospective study of human-milk composition. Mothers were enrolled from 3 urban populations with differing diets: Cincinnati, Ohio; Shanghai, China; and Mexico City, Mexico. Enrollment was limited to healthy mothers of term singleton infants. We undertook a cross-sectional analysis of milk from all women with samples at postpartum week 4 (n = 359; ∼120 women/site). Fatty acids were extracted from milk by using a modified Bligh-Dyer technique and analyzed by gas chromatography. Statistical analysis was performed by ANOVA and Tobit regression. For Cincinnati mothers, 24-h diet recalls were analyzed in relation to the individual BCFA concentrations measured in milk samples. RESULTS: Total BCFAs in milk differed by site, with the highest concentration in Cincinnati followed by Mexico City and Shanghai (mean ± SE: 7.90 ± 0.41, 6.10 ± 0.36, and 4.27 ± 0.25 mg/100 mL, respectively; P < 0.001). Site differences persisted after delivery mode, maternal age, and body mass index were controlled for. The individual concentrations of iso-14:0, iso-16:0, iso-18:0, anteiso-15:0, and anteiso-17:0 also differed between sites. Milk concentrations of iso-14:0 and anteiso-15:0 were associated with maternal intake of dairy; iso-16:0 was associated with maternal intakes of dairy and beef. CONCLUSIONS: BCFA concentrations in milk at 4 wk postpartum differed between mothers from Cincinnati, Shanghai, and Mexico City. Variations in human-milk BCFAs are influenced by diet. The impact of BCFAs on infant health warrants investigation.

Development of the Flu-PRO: a patient-reported outcome (PRO) instrument to evaluate symptoms of influenza.

BACKGROUND: To develop content validity of a comprehensive patient-reported outcome (PRO) measure following current best scientific methodology to standardize assessment of influenza (flu) symptoms in clinical research. METHODS: Stage I (Concept Elicitation): 1:1 telephone interviews with influenza-positive adults (≥18 years) in the US and Mexico within 7 days of diagnosis. Participants described symptom type, character, severity, and duration. Content analysis identified themes and developed the draft Flu-PRO instrument. Stage II (Cognitive Interviewing): The Flu-PRO was administered to a unique set of influenza-positive adults within 14 days of diagnosis; telephone interviews addressed completeness, respondent interpretation of items and ease of use. RESULTS: Samples: Stage I: N = 46 adults (16 US, 30 Mexico); mean (SD) age: 38 (19), 39 (14) years; % female: 56%, 73%; race: 69% White, 97% Mestizo. Stage II: N = 34 adults (12 US, 22 Mexico); age: 37 (14), 39 (11) years; % female: 50%, 50%; race: 58% White, 100% Mestizo. SYMPTOMS: Symptoms identified by >50%: coughing, weak or tired, throat symptoms, congestion, headache, weakness, sweating, chills, general discomfort, runny nose, chest (trouble breathing), difficulty sleeping, and body aches or pains. No new content was uncovered during Stage II; participants easily understood the instrument. CONCLUSIONS: Results show the 37-item Flu-PRO is a content valid measure of influenza symptoms in adults with a confirmed diagnosis of influenza. Research is underway to evaluate the suitability of the instrument for children and adolescents. This work can form the basis for future quantitative tests of reliability, validity, and responsiveness to evaluate the measurement properties of Flu-PRO for use in clinical trials and epidemiology studies.

Impact of formal training in endoscopic submucosal dissection for early gastrointestinal cancer: A systematic review and a meta-analysis.

AIM: To summarize the clinical impact of a formal training for the effectiveness and safety of endoscopic submucosal dissection for gastrointestinal cancer. METHODS: We searched databases including PubMed, EMBASE and the Cochrane Library and Science citation Index updated to August 2014 to include eligible articles. In the Meta-analysis, the main outcome measurements were en bloc resection rate, local recurrence rate (R0) and the incidence of procedure-related complications (perforation, bleeding). RESULTS: En bloc resection was high for both, dissecting stomach tumors with an overall percentage of 93.2% (95%CI: 90.5-95.8) and dissecting colorectal tumors with an overall percentage of 89.4% (95%CI: 85.1-93.7). Although the number of studies reporting R0 resection (the dissected specimen was revealed free of tumor in both vertical and lateral margins) was small, the overall estimates for R0 resection were 81.4% (95%CI: 72-90.8) for stomach and 85.9% (95%CI: 77.5-95.5) for colorectal tumors, respectively. The analysis showed that the percentage of immediate perforation and bleeding were very low; 4.96 (95%CI: 3.6-6.3) and 1.4% (95%CI: 0.8-1.9) for colorectal tumors and 3.1% (95%CI: 2.0-4.1) and 4.8% (95%CI: 2.8-6.7) for stomach tumors, respectively. CONCLUSION: In order to obtain the same rate of success of the analyzed studies it is a necessity to create training centers in the western countries during the "several years" of gastroenterology residence first only to teach EGC diagnose and second only to train endoscopic submucosal dissection.

Clinical characteristics and outcomes of influenza and other influenza-like illnesses in Mexico City.

BACKGROUND: Influenza-like illnesses (ILI) are estimated to cause millions of deaths annually. Despite this disease burden, the etiologic causes of ILI are poorly described for many geographical regions. METHODS: Beginning in April 2010, we conducted an observational cohort study at five hospitals in Mexico City, enrolling subjects who met the criteria for ILI. Evaluations were conducted at enrollment and on day 28, with the collection of clinical data and a nasopharyngeal swab (or nasal aspirate in children). Swabs were tested by multiplex PCR for 15 viral pathogens and real-time PCR for influenza. RESULTS: During the first year, 1065 subjects were enrolled in this study, 55% of whom were hospitalized; 24% of all subjects were children. One or more pathogens were detected by PCR in 64% of subjects, most commonly rhinovirus (25% of all isolates) and influenza (24% of isolates). Six percent of subjects died, and of those, 54% had no pathogen identified. Rhinovirus was the most common pathogen among those who died, although it did not have the highest case fatality rate. CONCLUSIONS: Multiple respiratory viruses beyond influenza are associated with significant morbidity and mortality among adults and children in Mexico City. Detection of these agents could be useful for the adjustment of antibiotic treatment in severe cases.

Prevalence of pneumococcal disease, serotype distribution, and antimicrobial susceptibility in Mexican children younger than 5 years of age.

BACKGROUND AND AIMS: Streptococcus pneumoniae constitutes one of the main causes of sepsis, bacteremia and meningitis (pneumococcal invasive disease - PID), and pneumonia in infants and small children. Antipneumococcal vaccination in Mexico is expected to be a useful strategy to reduce morbimortality due to this cause. We undertook this study to determine the prevalence of PID and pneumonia and the PCV vaccination status of affected children as well as serotype distribution and antimicrobial susceptibility of pneumococcal strains responsible for PID in infants and small children in Mexico. METHODS: From March 2010-June 2011, a prospective multicenter study was carried out in four states in Mexico to determine the prevalence of bacteremia, meningitis, septic arthritis and pneumonia due to S. pneumoniae and other microorganisms in children from 28 days-59 months of age. Isolated pneumococcal strains were serotyped and their antimicrobial resistance determined. RESULTS: During the study period, 545 children were diagnosed with bacteremia, meningitis, septic arthritis or pneumonia; 46.7% of these clinical entities occurred among children <12 months of age. Community-acquired pneumonia was the most prevalent disease. It was possible to identify a causal microorganism in 55 cases, from which 80% were S. pneumoniae. Fifteen percent of patients with PID died. The most prevalent pneumococcal serotypes were 19A, 35B, 19F and 6A. 10.2% of nonmeningeal strains were resistant to meropenem and 82% were resistant to TMP/SMX. CONCLUSIONS: This study shows that pneumococcus was the most common bacteria isolated in the studied population, although epidemiological and laboratory-based surveillance still needs improvement.

Immunogenicity and safety of a booster dose of the 10-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine coadministered with the tetravalent meningococcal serogroups A, C, W-135 and Y tetanus toxoid conjugate vaccine in toddlers: a randomized trial.

BACKGROUND: This open, randomized clinical trial (NCT00758264) evaluated the coadministration of a booster dose of the 10-valent pneumococcal conjugate vaccine (PHiD-CV) and a single dose of the tetravalent meningococcal conjugate vaccine (MenACWY-TT) in Taiwanese and Mexican toddlers. METHODS: Healthy toddlers aged 12-23 months (N = 363) were randomized (2:1:1) to receive either both vaccines at first visit, MenACWY-TT at first visit and 1 month later PHiD-CV, or PHiD-CV at first visit and 1 month later MenACWY-TT. Immune responses were measured 1 month after MenACWY-TT vaccination by meningococcal serum bactericidal activity (rSBA) assay and 1 month after PHiD-CV vaccination by pneumococcal 22F-inhibition enzyme-linked immunosorbent assay and functional opsonophagocytic activity assay. Solicited and unsolicited symptoms were recorded for days 4 and 31 postvaccination, respectively. Serious adverse events were recorded throughout the study. RESULTS: The prespecified criteria for noninferiority of coadministration versus individual administrations were met for all meningococcal serogroups (in terms of percentages of toddlers with rSBA titer ≥8) and all vaccine pneumococcal serotypes (in terms of antibody geometric mean concentration ratios), except pneumococcal serotype 18C. For each meningococcal serogroup, ≥97.5% of toddlers across the 3 groups had rSBA titers ≥128 at 1 month after MenACWY-TT vaccination. For each pneumococcal serotype, at 1 month after PHiD-CV vaccination, ≥96.0% and ≥92.9% of toddlers across the 3 groups had antibody concentrations ≥0.2 µg/mL and opsonophagocytic activity titers ≥8, respectively. The safety profiles of both vaccines when coadministered were clinically acceptable. CONCLUSIONS: This study supports the coadministration of PHiD-CV and MenACWY-TT in toddlers.

Specific infant feeding practices do not consistently explain variation in anthropometry at age 1 year in urban United States, Mexico, and China cohorts.

Infant feeding practices generally influence infant growth, but it is unclear how introduction of specific foods affects growth across global populations. We studied 3 urban populations in the Global Exploration of Human Milk study to determine the association between infant feeding and anthropometry at 1 y of age. Three hundred sixty-five breastfeeding mother-infant pairs (120 US, 120 China, and 125 Mexico) were recruited soon after the infant's birth. Enrollment required agreement to breastfeed ≥75% for at least 3 mo. Weekly, 24-h, food frequency data were conducted on infants for 1 y and exclusive breastfeeding (EBF) duration and timing of specific complementary food introduction were calculated. Weight and length were measured at age 1 y and anthropometry Z-scores calculated using WHO standards. Cohorts in the 3 urban populations (Shanghai, China; Cincinnati, USA; and Mexico City, Mexico) differed by median EBF duration (5, 14, and 7 wk, respectively; P < 0.001), timing of introduction of meat/eggs/legumes (4.8, 9.3, and 7.0 mo, respectively; P < 0.0001), and other feeding practices. By age 1 y, infants in Shanghai were heavier and longer than Cincinnati and Mexico City infants (P < 0.001). Adjusting for nonfeeding covariates, the only feeding variable associated with anthropometry was EBF duration, which was modestly inversely associated with weight-for-age but not length-for-age or BMI Z-scores at 1 y. Although feeding variables differed by cohort, their impact on anthropometry differences was not consistent among cohorts. Overall, across these urban, international, breast-fed cohorts, differences in specific feeding practices did not explain the significant variation in anthropometry.

Dose-range study of MF59-adjuvanted versus nonadjuvanted monovalent A/H1N1 pandemic influenza vaccine in six- to less than thirty-six-month-old children.

BACKGROUND: The successful vaccination of children 6 to 36 months of age against 2009 A/H1N1 influenza was essential to help reduce the burden of pandemic disease in both the pediatric and adult populations. OBJECTIVES: We compared the immunogenicity and safety of 4 alternative monovalent vaccine formulations to identify which provided optimal levels of seroprotection according to the US and European Union (EU) licensure criteria. SUBJECTS AND METHODS: A total of 654 healthy subjects (6 to <36 months old) were given 2 vaccine doses 3 weeks apart. Participants were assigned to 1 of the 4 immunization groups, receiving MF59-adjuvanted (Novartis Vaccines, Marburg, Germany) vaccine either containing 3.75 µg or 7.5 µg of A/H1N1 California/7/2009 antigen, or nonadjuvanted vaccine containing 7.5 µg or 15 µg of antigen. Antibody titers were assessed by hemagglutination inhibition assay 3 weeks, 3 months and 1 year after immunization. Vaccine safety was monitored throughout the study. RESULTS: After 1 dose, both adjuvanted formulations met the US and EU criteria for seroconversion; the 15 µg nonadjuvanted vaccine met the EU criterion for seroconversion alone. The US and EU criteria for seroprotection were only met by adjuvanted groups. MF59-adjuvanted formulations alone resulted in clinically significant persisting antibody titers after 12 months. All vaccines were well tolerated. CONCLUSIONS: A single dose of MF59-adjuvanted vaccine containing 3.75 µg A/H1N1 antigen was highly immunogenic, met both the US and EU licensure criteria and was well tolerated. These data support the suitability of this monovalent vaccine formulation for pandemic use in children 6 to <36 months of age.

Human milk adiponectin affects infant weight trajectory during the second year of life.

OBJECTIVE: Serum adiponectin (APN) is associated with lower childhood obesity, and APN concentration in human milk is associated with slower growth during active breast-feeding. We examined infant weight gain in the second year of life after exposure to high or low levels of mother's milk APN. METHODS: Breast-feeding mother-infant pairs were recruited in Mexico City and studied for 2 years; 192 infants with at least 12 months' follow-up were analyzed. Monthly milk samples were assayed for APN; mothers were classified as producing high or low levels of milk APN. Infant and maternal serum APN were assessed during year 1. Infant anthropometry was measured monthly (year 1) or bimonthly (year 2), and World Health Organization z scores were calculated. Longitudinal adjusted models assessed weight-for-age and weight-for-length z score trajectories from 1 to 2 years. RESULTS: Maternal serum APN modestly correlated with milk APN (r=0.37, P<0.0001) and infant serum APN (r=0.29, P=0.01). Infants exposed to high milk APN experienced increasing weight-for-age and weight-for-length z scores between age 1 and 2 years in contrast to low milk APN exposure (P for group × time=0.02 and 0.054, respectively), adjusting for growth in the first 6 months and other covariates. In contrast, infant serum APN in year 1 was not associated with the rate of weight gain in year 2. CONCLUSIONS: High human milk APN exposure was associated with accelerated weight trajectory during the second year of life, suggesting its role in catch-up growth after slower weight gain during the first year of life.

Immunogenicity, reactogenicity and safety of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in Mexican infants.

The immunogenicity and safety of the 10-valent pneumococcal conjugate vaccine, PHiD-CV, have been documented in European and Asian studies. In this open study conducted in Mexico (NCT00489554), 230 healthy infants received three doses of PHiD-CV and DTPa-HBV-IPV/Hib vaccines at 2, 4 and 6 months of age and two doses of oral human rotavirus vaccine at 2 and 4 months. Serotype-specific pneumococcal responses and opsonophagocytic activity (OPA) were measured one month post-dose 3. PHiD-CV's primary vaccination course was highly immunogenic against each of the 10 pneumococcal vaccine serotypes and carrier protein D. Antibody responses against pneumococcal serotypes and protein D were generally higher in Mexican infants compared with European antibody responses, and functional OPA responses were also higher or in the same range. The most frequent solicited local symptom was pain, with high but similar incidences of grade 3 pain reported at both injection sites (up to 15% of all doses). PHiD-CV was well tolerated, with no serious adverse events considered as causally related to vaccination. Most solicited symptoms were mild and there was no increase in incidence of solicited symptoms with successive vaccine doses.

Human milk adiponectin is associated with infant growth in two independent cohorts.

BACKGROUND: Adiponectin, a circulating adipocyte protein, is associated with lower obesity. We have previously shown that adiponectin is present in human milk. This study determined whether higher milk adiponectin is associated with infant growth and investigated milk adiponectin's oligomeric form. DESIGN AND METHODS: This is a study of two parallel longitudinal cohorts of breastfed infants born between 1998 and 2005. Forty-five mother-infant pairs from Cincinnati, OH and 277 mother-infant pairs from Mexico City, Mexico were analyzed. All participants were healthy, term infants breastfed at least 1 month who completed 6 months of follow-up. Monthly milk samples (n = 1,379) up to 6 months were assayed for adiponectin by radioimmunoassay. Infant weight-for-age, length-for-age, and weight-for-length Z-scores up to 6 months of age were calculated using World Health Organization standards. Repeated-measures analysis was conducted. The structural form of human milk adiponectin was assessed by western blot. RESULTS: In the population studies, initial milk adiponectin was 24.0 +/- 8.6 microg/L and did not differ by cohort. Over the first 6 months, higher milk adiponectin was associated with lower infant weight-for-age Z-score (-0.20 +/- 0.04, p < 0.0001) and weight-for-length Z-score (-0.29 +/- 0.08, p = 0.0002) but not length-for-age Z-score, adjusted for covariates, with no difference by cohort. By western blot, human milk adiponectin was predominantly in the biologically active high-molecular-weight form. CONCLUSIONS: Our data suggest milk adiponectin may play a role in the early growth and development of breastfed infants.

Improving outcome of human immunodeficiency virus-infected patients in a Mexican intensive care unit.

BACKGROUND: In Latin America, insufficient data are available to improve local admission policies for human immunodeficiency virus (HIV) patients in the intensive care units (ICU). We undertook this study to evaluate the outcome and survival determinants of HIV patients in a Mexican ICU during three time periods. METHODS: From December 1985 through January 2006, a clinical chart-based, retrospective study of all HIV patients admitted to the ICU was conducted. Demographic, clinical and laboratory data; disease severity score (APACHE II) and mortality were evaluated. A comprehensive database was created and data were analyzed using survival and regression models. RESULTS: Ninety HIV patients were admitted to the ICU during the study: 16 (18%) in 1985-1992 (non-antiretroviral [ARV]-period), 21 (23%) in 1993-1996 (ARV-period), and 53 (58%) in 1996-2006 (highly active antiretroviral treatment [HAART] period). Leading reasons for admission were the need for mechanical ventilatory support (MVS, 85.5%), septic shock (23%), and non-HIV/AIDS complications (15.5%). Survival in the ICU increased from 12.5% (non-ARV period) to 57% (HAART period). Mortality during ICU stay was associated with MVS (HR: 3.2; 95% CI 1.0-10.2) and APACHE II > or =13 points (HR: 2.2; 95% CI 1.3-4.0). Use of steroids (HR: 0.4; 95% CI 0.2-0.8) and HAART (HR: 0.25; 95% CI 0.1-0.5) were associated with a lower risk of death. In multivariate analysis, septic shock was the main predictor of death in the ICU (HR: 2.4; 95% CI 1.1-5.2) and after discharge. HAART remained as a significant protective factor. CONCLUSIONS: Overall survival in Mexican HIV patients admitted to an ICU has substantially increased in recent years. These data should encourage policies that consider HIV patients as good candidates for receiving intensive care.