Streptococcus pneumoniae serotype 3 population structure in the era of conjugate vaccines, 2001-2018.

Background. Despite use of highly effective conjugate vaccines, invasive pneumococcal disease (IPD) remains a leading cause of morbidity and mortality and disproportionately affects Indigenous populations. Although included in the 13-valent pneumococcal conjugate vaccine (PCV13), which was introduced in 2010, serotype 3 continues to cause disease among Indigenous communities in the Southwest USA. In the Navajo Nation, serotype 3 IPD incidence increased among adults (3.8/100 000 in 2001-2009 and 6.2/100 000 in 2011-2019); in children the disease persisted although the rates dropped from 5.8/100 000 to 2.3/100 000.Methods. We analysed the genomic epidemiology of serotype 3 isolates collected from 129 adults and 63 children with pneumococcal carriage (n=61) or IPD (n=131) from 2001 to 2018 of the Navajo Nation. Using whole-genome sequencing data, we determined clade membership and assessed changes in serotype 3 population structure over time.Results. The serotype 3 population structure was characterized by three dominant subpopulations: clade II (n=90, 46.9 %) and clade Iα (n=59, 30.7 %), which fall into Clonal Complex (CC) 180, and a non-CC180 clade (n=43, 22.4 %). The proportion of clade II-associated IPD cases increased significantly from 2001 to 2010 to 2011-2018 among adults (23.1-71.8 %; P<0.001) but not in children (27.3-33.3 %; P=0.84). Over the same period, the proportion of clade II-associated carriage increased; this was statistically significant among children (23.3-52.6 %; P=0.04) but not adults (0-50.0 %, P=0.08).Conclusions. In this setting with persistent serotype 3 IPD and carriage, clade II has increased since 2010. Genomic changes may be contributing to the observed trends in serotype 3 carriage and disease over time.

Characterization of Blighia sapida seed extracts.

Blighia sapida, commonly known as the ackee, is a member of the Sapindaceae family. The tree is native to the forests of West Africa and was brought to the Caribbean and later Florida, where it is cultivated as an orchard crop in some areas. Arilli of the fruit are processed to make canned ackee in brine whereas the seeds, raphe and pods are discarded. Physiochemical studies were conducted on extracts of the seed. Qualitative analysis detected the presence of phenolics and reducing sugars. Aqueous extracts of the seeds (ASE) exhibited free radical scavenging activity and had an inhibitory concentration of 2.59 mg/mL. Gas chromatography mass spectrometry led to the identification of several metabolites including amino acids and fatty acids. Hypoglycin B was isolated utilizing ion exchange chromatography. Fourier transform infrared spectroscopy of hypoglycin B detected a band resonating at 3070 cm-1 which may be attributed to the methylenecyclopropane moiety of hypoglycin B. The seeds had a lipid content of 5.72 ± 0.25 % (w/w). The ackee seed oil (ASO) had a saponification value of 152.07 ± 37 and a carotenoid content of 23.7 ± 1.8 mg/kg. The ackee seeds are a source of bioactive components.

Evaluation of indoor PM2.5 concentrations in a Native American Community: a pilot study.

BACKGROUND: Indoor air pollution is associated with adverse health effects; however, few studies exist studying indoor air pollution on the Navajo Nation in the southwest U.S., a community with high rates of respiratory disease. METHODS: Indoor PM2.5 concentration was evaluated in 26 homes on the Navajo Nation using real-time PM2.5 monitors. Household risk factors and daily activities were evaluated with three metrics of indoor PM2.5: time-weighted average (TWA), 90th percentile of concentration, and daily minutes exceeding 100 µg/m3. A questionnaire and recall sheet were used to record baseline household characteristics and daily activities. RESULTS: The median TWA, 90th percentile, and daily minutes exceeding 100 µg/m3 were 7.9 µg/m3, 14.0 µg/m3, and 17 min, respectively. TWAs tended to be higher in autumn and in houses that used fuel the previous day. Other characteristics associated with elevated PM exposure in all metrics included overcrowded houses, nonmobile houses, and houses with current smokers, pets, and longer cooking time. CONCLUSIONS: Some residents of the Navajo Nation have higher risk of exposure to indoor air pollution by Environmental Protection Agency (EPA) standards. Efforts to identify the causes and associations with adverse health effects are needed to ensure that exposure to risks and possible health impacts are mitigated.

Empowering Native Adolescents: Responsibility for Their Health Behaviors.

Objectives: In this study, we assess the impact of a home-based diabetes prevention program, Together on Diabetes (TOD), on adolescent responsibility-taking for tasks related to diabetes risk. Methods: Participants were Native American youth ages 10-19 with or at risk of type 2 diabetes who participated in a 12-session, 6-month diabetes prevention program with an adult caretaker. Assessments completed at baseline, 6-month, and 12-month follow-up include demographics and the Diabetes and Obesity Task Sharing (DOTS) Questionnaire. We used latent class analysis (LCA) at baseline to examine heterogeneity in DOTS responses. We identified 3 classes (adolescent, shared, caretaker). We used latent transition analysis to examine stability and change in latent status at baseline, 6- and 12-month follow-up. Results: At baseline, the mean age of participants was 13.6 years and 55.9% were boys. From baseline to 6-month follow-up, the adolescent class was most stable, whereas the shared and caretaker classes were less stable. For participants who transition from the adolescent class, most transition to shared class compared to caretaker class. Conclusions: TOD helps to empower Native American adolescents to take responsibility for their health and engage with their caregivers in these decisions.

Effect of a Home-Visiting Intervention to Reduce Early Childhood Obesity Among Native American Children: A Randomized Clinical Trial.

Importance: Early childhood obesity disproportionately affects Native American communities. Home visiting is a promising strategy for promoting optimal infant growth in this population. Objective: To assess the impact of a brief home-visiting approach, Family Spirit Nurture (FSN), on sugar-sweetened beverage (SSB) consumption, responsive parenting and infant feeding practices, and optimal growth through 12 months post partum. Design, Setting, and Participants: This study was a 1:1 randomized clinical trial comparing FSN with an injury prevention education control condition in a reservation-based community. Participants were Navajo mothers 13 years or older with infants younger than 14 weeks recruited between March 22, 2017, and May 18, 2018, and followed up through 12 months post partum. Intent-to-treat analyses were conducted. Interventions: The 6-lesson FSN curriculum, delivered 3 to 6 months post partum by Navajo paraprofessionals, targeted optimal responsive and complementary feeding practices and avoidance of SSBs. The control group received 3 injury prevention lessons. Main Outcomes and Measures: Primary outcomes established a priori were infant SSB consumption and responsive parenting and complementary feeding practices (responsive feeding scale, age at complementary food introduction, and percentage of mothers who introduced complementary food to infants at 6 months of age or older). The secondary outcome was the effect of the intervention on infant body mass index z scores (zBMIs). Results: A total of 134 Navajo mothers of infants younger than 14 weeks were enrolled in the randomized clinical trial, including 68 (mean [SD] maternal age at enrollment, 27.4 [6.4] years) in the intervention group and 66 (mean [SD] maternal age at enrollment, 27.5 [6.1] years) in the control group. Intervention participants reported statistically significantly lower infant SSB consumption through 12 months post partum (mean [SE], 0.56 [0.12] cups per week in the intervention group and 1.78 [0.18] cups per week in the control group; incidence rate ratio, 0.31; 95% CI, 0.19-0.50). Improvements in responsive feeding practices were observed through 9 months post partum (mean [SE], 3.48 [0.07] in the intervention group and 3.22 [0.08] in the control group) (difference, 0.26; 95% CI, 0.06-0.47); statistical significance was lost at 12 months post partum. Age at which the infant was given first food was younger in the intervention group (mean [SE] age, 4.61 [0.21] months in the intervention group and 5.28 [0.23] months in the control group) (difference, -0.67; 95% CI, -0.04 to -1.29). Infants in the intervention group had lower zBMI at 6 and 9 months compared with those in the control group (mean [SE] at 9 months, 0.27 [0.14] in the intervention group and 0.81 [0.14] in the control group; difference, -0.54; 95% CI, -0.94 to -0.14). The 12-month between-group difference was meaningful but not statistically significant (mean [SE], 0.61 [0.16] in the intervention group and 1.07 [0.20] in the control group; difference, -0.46; 95% CI, -0.92 to 0.01). Conclusions and Relevance: Infants of Native American mothers who participated in a home-visiting intervention had substantially lower SSB consumption and improvements in responsive feeding practices and infant zBMI scores, suggesting the intervention is effective for promoting healthy infant feeding and growth. Trial Registration: ClinicalTrials.gov Identifier: NCT03101943.

Centering the Strengths of American Indian Culture, Families and Communities to Overcome Type 2 Diabetes.

Type 2 diabetes (T2D) is a critical Indigenous health inequity rooted in experiences of colonization and marginalization including disproportionate exposure to stressors, disruption of traditional family and food systems, and attacks on cultural practices that have led to more sedentary lifestyles. Thus, an important step in redressing inequities is building awareness of and interventions attuned to unique Indigenous contexts influencing T2D and Indigenous culture as a pathway to community wellbeing. Using a dynamic, stage-based model of intervention development and evaluation, we detail the creation and evolution of a family-based, culturally centered T2D preventive intervention: Together on Diabetes (later Together Overcoming Diabetes) (TOD). The TOD program was built by and for Indigenous communities via community-based participatory research and has been implemented across diverse cultural contexts. The TOD curriculum approaches health through a holistic lens of spiritual, mental, physical and emotional wellness. Preliminary evidence suggests TOD is effective in reducing diabetes risk factors including lowering BMI and depressive symptoms, and the program is viewed favorably by participants and community members. We discuss lessons learned regarding collaborative intervention development and adaptation across Indigenous cultures, as well as future directions for TOD.

Frequency-dependent selection can forecast evolution in Streptococcus pneumoniae.

Predicting how pathogen populations will change over time is challenging. Such has been the case with Streptococcus pneumoniae, an important human pathogen, and the pneumococcal conjugate vaccines (PCVs), which target only a fraction of the strains in the population. Here, we use the frequencies of accessory genes to predict changes in the pneumococcal population after vaccination, hypothesizing that these frequencies reflect negative frequency-dependent selection (NFDS) on the gene products. We find that the standardized predicted fitness of a strain, estimated by an NFDS-based model at the time the vaccine is introduced, enables us to predict whether the strain increases or decreases in prevalence following vaccination. Further, we are able to forecast the equilibrium post-vaccine population composition and assess the invasion capacity of emerging lineages. Overall, we provide a method for predicting the impact of an intervention on pneumococcal populations with potential application to other bacterial pathogens in which NFDS is a driving force.

Efficacy, safety and immunogenicity of a pneumococcal protein-based vaccine co-administered with 13-valent pneumococcal conjugate vaccine against acute otitis media in young children: A phase IIb randomized study.

BACKGROUND: Native American populations experience a substantial burden of pneumococcal disease despite use of highly effective pneumococcal conjugate vaccines (PCVs). Protein-based pneumococcal vaccines may extend protection beyond the serotype-specific protection elicited by PCVs. METHODS: In this phase IIb, double-blind, controlled trial, 6-12 weeks-old Native American infants randomized 1:1, received either a protein-based pneumococcal vaccine (dPly/PhtD) containing pneumolysin toxoid (dPly, 10 µg) and pneumococcal histidine triad protein D (PhtD, 10 µg) or placebo, administered along with 13-valent PCV (PCV13) at ages 2, 4, 6 and 12-15 months. Other pediatric vaccines were given per the routine immunization schedule. We assessed vaccine efficacy (VE) against acute otitis media (AOM) and acute lower respiratory tract infection (ALRI) endpoints. Immunogenicity, reactogenicity and unsolicited adverse events were assessed in a sub-cohort and serious adverse events were assessed in all children. RESULTS: 1803 infants were randomized (900 dPly/PhtD; 903 Control). VE against all episodes of American Academy of Pediatrics (AAP)-defined AOM was 3.8% (95% confidence interval: -11.4, 16.9). Point estimates of VE against other AOM outcomes ranged between 2.9% (-9.5, 14.0) and 5.2% (-8.0, 16.8). Point estimates of VE against ALRI outcomes ranged between -4.4% (-39.2, 21.8) and 2.0% (-18.3, 18.8). Point estimates of VE tended to be higher against first than all episodes but the confidence intervals included zero. dPly/PhtD vaccine was immunogenic and had an acceptable reactogenicity and safety profile after primary and booster vaccination in Native American infants. CONCLUSIONS: The dPly/PhtD vaccine was immunogenic and well tolerated, however, incremental efficacy in preventing AAP-AOM over PCV13 was not demonstrated. CLINICAL TRIALS REGISTRATION: NCT01545375 (www.clinicaltrials.gov).

Association of Laboratory Methods, Colonization Density, and Age With Detection of Streptococcus pneumoniae in the Nasopharynx.

Culture-based methods for detecting Streptococcus pneumoniae in the nasopharynx lack sensitivity. In this study, we aimed to compare the performance of culture and molecular methods in detecting pneumococcus in the nasopharynx of healthy individuals and to evaluate the associations of age and colonization density with detection. Between 2010 and 2012, nasopharyngeal specimens were collected from healthy individuals living on Navajo Nation and White Mountain Apache Tribal lands in the United States. Pneumococci were detected by means of broth-enrichment culture and autolysin-encoding gene (lytA) quantitative polymerase chain reaction (qPCR). Among 982 persons evaluated (median age, 18.7 years; 47% male), 35% were culture-positive and an additional 27% were qPCR-positive. Agreement between culture and qPCR was 70.9% but was higher among children (age <18 years) (75.9%-84.4%) than among adults (age ≥18 years) (61.0%-74.6%). The mean density of colonization was lower for culture-negative samples (3.14 log10 copies/mL) than for culture-positive samples (5.02 log10 copies/mL), overall and for all age groups. The percent culture-positive increased with increasing density, exceeding 80% at densities of ≥10,000 copies/mL. Mean colonization density decreased with age. Use of qPCR improved detection of pneumococcus in the nasopharynx of healthy individuals. This finding was most notable among adults, probably because of improved detection of low-density colonization.

Family Spirit Nurture (FSN) - a randomized controlled trial to prevent early childhood obesity in American Indian populations: trial rationale and study protocol.

BACKGROUND: Childhood overweight and obesity is a persistent public health issue in the US. Risk for obesity and obesity-related morbidity throughout the life course begins in utero. Native Americans suffer the greatest disparities in the US in childhood overweight and obesity status of any racial or ethnic group. Existing early childhood home-visiting interventions provide an opportunity for addressing obesity during the first 1000 days. However, to date, no evidence-based model has been specifically designed to comprehensively target early childhood obesity prevention. METHODS: This study is a randomized controlled trial to test the efficacy of home-visiting intervention, called Family Spirit Nurture, on reducing early childhood obesity in Native American children. Participants are expectant Native American mothers ages 14-24 and their child, enrolled from pregnancy to 24 months postpartum and randomized 1:1 to receive the Family Spirit Nurture intervention or a control condition. The intervention includes 36 lessons delivered one-on-one by locally-hired Native American Family Health Coaches to participating mothers from pregnancy until 18 months postpartum. A mixed methods assessment includes maternal self-reports, maternal and child observations, and physical and biological data collected at 11 time points from 32 weeks gestation to 2 years postpartum to measure the intervention's primary impact on maternal feeding behaviors; children's healthy diet and physical activity; children's weight status. Secondary measures include maternal psychosocial factors; household food and water security; infant sleep and temperament; and maternal and child metabolic status. DISCUSSION: None of the 20 current federally-endorsed home-visiting models have demonstrated impacts on preventing early childhood obesity. The original Family Spirit program, upon which Family Spirit Nurture is based, demonstrated effect on maternal and child behavioral health, not including obesity related risk factors. This trial has potential to inform the effectiveness of home-visiting intervention to reduce obesity risk for tribal communities and other vulnerable populations and expand public health solutions for the world's obesity crisis. TRIAL REGISTRATION: Clinicaltrials.gov (Identifier: NCT03334266 - Preventing Early Childhood Obesity, Part 2: Family Spirit Nurture, Prenatal - 18 Months; Retrospectively registered on 07 November 2017).

The burden of Staphylococcus aureus among Native Americans on the Navajo Nation.

INTRODUCTION: Native Americans in the southwestern United States have a higher risk for many infectious diseases and may be at higher risk for Staphylococcus aureus due to the high prevalence of risk factors for S. aureus. Recent data on invasive S. aureus infections among Native Americans are limited. METHODS: Active population- and laboratory-based surveillance was conducted in 2016-2017 on the Navajo Nation to document the rate of invasive S. aureus. A case of invasive S.aureus infection was defined as a Native American individual with S. aureus isolated from a normally sterile body site whose reported community of residence was on or around the Navajo Nation. RESULTS: One hundred and fifty-nine cases of invasive S. aureus from 152 individuals were identified. The median age of cases was 56.3 years and 35% were female. Thirty-five percent of cases had community-acquired infections. Ninety-three percent of cases had underlying medical conditions, including diabetes (60%) and obesity (42%), 28% of cases had a documented prior S. aureus infection, and 33% were infected with methicillin-resistant S. aureus. The annual incidence of invasive S. aureus and of invasive methicillin-resistant S. aureus was 64.9/100,000 persons and 21.2/100,000 persons, respectively. CONCLUSIONS: This community has a high burden of invasive S. aureus infections. Further research is needed to identify prevention strategies and opportunities for intervention.

Water quality, availability, and acute gastroenteritis on the Navajo Nation - a pilot case-control study.

The Navajo Nation includes approximately 250,000 American Indians living in a remote high desert environment with limited access to public water systems. We conducted a pilot case-control study to assess associations between acute gastroenteritis (AGE) and water availability, use patterns, and quality. Case patients with AGE and non-AGE controls who presented for care to two Indian Health Service hospitals were recruited. Data on demographics and water use practices were collected using a standard questionnaire. Household drinking water was tested for presence of pathogens, coliforms, and residual chlorine. Sixty-one subjects (32 cases and 29 controls) participated in the study. Cases and controls were not significantly different with respect to water sources, quality, or patterns of use. Twenty-one percent (n = 12) of study participants resided in dwellings not connected to a community water system. Eleven percent (n = 7) of subjects reported drinking hauled water from unregulated sources. Coliform bacteria were present in 44% (n = 27) of household water samples, and 68% (n = 40) of samples contained residual chlorine concentrations of <0.2 mg/L. This study highlights issues with water availability, quality, and use patterns within the Navajo Nation, including sub-optimal access to community water systems, and use of water hauled from unregulated sources.

Global emergence and population dynamics of divergent serotype 3 CC180 pneumococci.

Streptococcus pneumoniae serotype 3 remains a significant cause of morbidity and mortality worldwide, despite inclusion in the 13-valent pneumococcal conjugate vaccine (PCV13). Serotype 3 increased in carriage since the implementation of PCV13 in the USA, while invasive disease rates remain unchanged. We investigated the persistence of serotype 3 in carriage and disease, through genomic analyses of a global sample of 301 serotype 3 isolates of the Netherlands3-31 (PMEN31) clone CC180, combined with associated patient data and PCV utilization among countries of isolate collection. We assessed phenotypic variation between dominant clades in capsule charge (zeta potential), capsular polysaccharide shedding, and susceptibility to opsonophagocytic killing, which have previously been associated with carriage duration, invasiveness, and vaccine escape. We identified a recent shift in the CC180 population attributed to a lineage termed Clade II, which was estimated by Bayesian coalescent analysis to have first appeared in 1968 [95% HPD: 1939-1989] and increased in prevalence and effective population size thereafter. Clade II isolates are divergent from the pre-PCV13 serotype 3 population in non-capsular antigenic composition, competence, and antibiotic susceptibility, the last of which resulting from the acquisition of a Tn916-like conjugative transposon. Differences in recombination rates among clades correlated with variations in the ATP-binding subunit of Clp protease, as well as amino acid substitutions in the comCDE operon. Opsonophagocytic killing assays elucidated the low observed efficacy of PCV13 against serotype 3. Variation in PCV13 use among sampled countries was not independently correlated with the CC180 population shift; therefore, genotypic and phenotypic differences in protein antigens and, in particular, antibiotic resistance may have contributed to the increase of Clade II. Our analysis emphasizes the need for routine, representative sampling of isolates from disperse geographic regions, including historically under-sampled areas. We also highlight the value of genomics in resolving antigenic and epidemiological variations within a serotype, which may have implications for future vaccine development.

The impact of serotype-specific vaccination on phylodynamic parameters of Streptococcus pneumoniae and the pneumococcal pan-genome.

In the United States, the introduction of the heptavalent pneumococcal conjugate vaccine (PCV) largely eliminated vaccine serotypes (VT); non-vaccine serotypes (NVT) subsequently increased in carriage and disease. Vaccination also disrupts the composition of the pneumococcal pangenome, which includes mobile genetic elements and polymorphic non-capsular antigens important for virulence, transmission, and pneumococcal ecology. Antigenic proteins are of interest for future vaccines; yet, little is known about how the they are affected by PCV use. To investigate the evolutionary impact of vaccination, we assessed recombination, evolution, and pathogen demographic history of 937 pneumococci collected from 1998-2012 among Navajo and White Mountain Apache Native American communities. We analyzed changes in the pneumococcal pangenome, focusing on metabolic loci and 19 polymorphic protein antigens. We found the impact of PCV on the pneumococcal population could be observed in reduced diversity, a smaller pangenome, and changing frequencies of accessory clusters of orthologous groups (COGs). Post-PCV7, diversity rebounded through clonal expansion of NVT lineages and inferred in-migration of two previously unobserved lineages. Accessory COGs frequencies trended toward pre-PCV7 values with increasing time since vaccine introduction. Contemporary frequencies of protein antigen variants are better predicted by pre-PCV7 values (1998-2000) than the preceding period (2006-2008), suggesting balancing selection may have acted in maintaining variant frequencies in this population. Overall, we present the largest genomic analysis of pneumococcal carriage in the United States to date, which includes a snapshot of a true vaccine-naïve community prior to the introduction of PCV7. These data improve our understanding of pneumococcal evolution and emphasize the need to consider pangenome composition when inferring the impact of vaccination and developing future protein-based pneumococcal vaccines.

Norovirus and Sapovirus Epidemiology and Strain Characteristics among Navajo and Apache Infants.

Norovirus and sapovirus are important causes of acute gastroenteritis (AGE) among American Indian infants. We investigated the prevalence and molecular epidemiology of norovirus and sapovirus in American Indian infants who have historically experienced a high burden of AGE compared to other US populations. Stool samples were collected from 241 children with AGE (cases) and from 343 infants without AGE (controls) ≤9 months of age from 2002-2004. Cases experienced forceful vomiting and/or 3 or more watery or looser-than-normal stools in 24 hours. Stools were tested by real-time RT-PCR for norovirus GI, GII and GIV and sapovirus GI, GII, GIV and GV. Positive samples were genotyped after sequencing conventional RT-PCR products. Norovirus was identified in 76 (31.5%) of the cases and 70 (20.4%) of the controls (p<0.001). GII.3 and GII.4 Farmington Hills were the most frequently identified genotypes in 14.5% and 30.3% of cases and 17.1% and 27.1% of controls, respectively. Sapovirus GI and GII genotypes were identified in 8 (3.3%) of cases and 8 (2.3%) of controls and a single GIV virus was detected in a control. The same norovirus and sapovirus genotypes were circulating in the general U.S. population in the same time period. The high detection rate of norovirus in healthy controls suggests significant asymptomatic transmission in young infants in these communities.

Association of Pneumococcal Protein Antigen Serology With Age and Antigenic Profile of Colonizing Isolates.

Background: Several Streptococcus pneumoniae proteins play a role in pathogenesis and are being investigated as vaccine targets. It is largely unknown whether naturally acquired antibodies reduce the risk of colonization with strains expressing a particular antigenic variant. Methods: Serum immunoglobulin G (IgG) titers to 28 pneumococcal protein antigens were measured among 242 individuals aged <6 months-78 years in Native American communities between 2007 and 2009. Nasopharyngeal swabs were collected >- 30 days after serum collection, and the antigen variant in each pneumococcal isolate was determined using genomic data. We assessed the association between preexisting variant-specific antibody titers and subsequent carriage of pneumococcus expressing a particular antigen variant. Results: Antibody titers often increased across pediatric groups before decreasing among adults. Individuals with low titers against group 3 pneumococcal surface protein C (PspC) variants were more likely to be colonized with pneumococci expressing those variants. For other antigens, variant-specific IgG titers do not predict colonization. Conclusion: We observed an inverse association between variant-specific antibody concentration and homologous pneumococcal colonization for only 1 protein. Further assessment of antibody repertoires may elucidate the nature of antipneumococcal antibody-mediated mucosal immunity while informing vaccine development.

The Impact of a Home-Based Diabetes Prevention and Management Program on High-Risk American Indian Youth.

PURPOSE: The purpose of this study was to examine the impact of a home-based diabetes prevention and management program on high-risk American Indian youth. METHODS: Together on Diabetes (TOD) was designed via a participatory approach with 4 tribal communities in the southwestern United States. A multisite pre- and postevaluation design was used to evaluate the efficacy of the TOD intervention on improving youth's psychosocial, knowledge, behavioral, and physiological outcomes at 4 time points from baseline to 12 months postenrollment. RESULTS: A total of 256 youth and 225 support persons were enrolled in the TOD program. At 12 months postenrollment, improvements were observed in youth's quality of life (P < .001), depressive symptoms (P < .001), knowledge related to TOD content (P < .001), standardized body mass index scores (P = .004), and hypertension (P = .026). Improvements in mean A1C were observed among diabetic youth with baseline A1C >6.5% (P = .036). CONCLUSIONS: The TOD program was feasible, acceptable, and effective in lowering diabetes risk among reservation-based American Indian youth. It is the first efficacious youth-focused diabetes prevention and management program developed and implemented in partnership with tribal communities.

Impact of the 13-Valent Pneumococcal Conjugate Vaccine on Pneumococcal Carriage Among American Indians.

BACKGROUND: Community-wide impact of pneumococcal conjugate vaccines (PCV) is conferred by reductions in vaccine-type nasopharyngeal carriage. We evaluated the impact of PCV13 on carriage of PCV13-specific types (1, 3, 5, 6A, 7F and 19A) and 6C among American Indians. METHODS: A nasopharyngeal specimen was collected from community members of all ages between January 2010 and April 2012 (3 months before and 24 months after PCV13 introduction). Pneumococci were isolated by culture and serotyped using antisera. Monthly carriage prevalence and PCV13 coverage were calculated to identify the timing of vaccine impact relative to PCV13 introduction. Prevalence ratios (PRs) were used to compare PCV13-specific carriage before and in years 1 and 2 of PCV13 use. Coverage was calculated according to age and number of doses received. RESULTS: 6645 participants (2859 <5 years and 3786 ≥5 years of age) provided 6628 specimens. A decline in PCV13-specific and type 6C carriage among children <5 years of age was observed 9 and 15 months after PCV13 introduction, respectively. Among underimmunized children, a decline in PCV13-specific carriage was observed 11 months after PCV13 introduction, when coverage in the community reached 58%. In year 2 of PCV13 use, PCV13-specific and 6C carriage were reduced by 60% and 70%, respectively (PCV13 specific: PR = 0.4, P < 0.001; 6C: PR = 0.3, P < 0.001) among children <5 years of age. The reduction in PCV13-specific carriage among those 5 to <8 years and 18+ years of age in year 2 of PCV13 use was not statistically significant. CONCLUSIONS: PCV13 reduced PCV13-specific and 6C carriage among children <5 years of age. Low pre-PCV13 carriage prevalence of PCV13-specific types limited confirming this reduction for adults.